BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis
Enhancers, critical determinants of cellular identity, are commonly recognized by correlative chromatin marks and gain-of-function potential, although only loss-of-function studies can demonstrate their requirement in the native genomic context. Previously, we identified an erythroid enhancer of hum...
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| Published in | Nature (London) Vol. 527; no. 7577; pp. 192 - 197 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
12.11.2015
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Enhancers, critical determinants of cellular identity, are commonly recognized by correlative chromatin marks and gain-of-function potential, although only loss-of-function studies can demonstrate their requirement in the native genomic context. Previously, we identified an erythroid enhancer of human
BCL11A
, subject to common genetic variation associated with the fetal haemoglobin level, the mouse orthologue of which is necessary for erythroid BCL11A expression. Here we develop pooled clustered regularly interspaced palindromic repeat (CRISPR)-Cas9 guide RNA libraries to perform
in situ
saturating mutagenesis of the human and mouse enhancers. This approach reveals critical minimal features and discrete vulnerabilities of these enhancers. Despite conserved function of the composite enhancers, their architecture diverges. The crucial human sequences appear to be primate-specific. Through editing of primary human progenitors and mouse transgenesis, we validate the
BCL11A
erythroid enhancer as a target for fetal haemoglobin reinduction. The detailed enhancer map will inform therapeutic genome editing, and the screening approach described here is generally applicable to functional interrogation of non-coding genomic elements.
A CRISPR-Cas9 approach is used to perform saturating mutagenesis of the human and mouse
BCL11A
enhancers, producing a map that reveals critical regions and specific vulnerabilities;
BCL11A
enhancer disruption is validated by CRISPR-Cas9 as a therapeutic strategy for inducing fetal haemoglobin by applying it in both mice and primary human erythroblast cells.
BCL11A
enhancer disruption analysed
BCL11A is a transcriptional repressor that inhibits expression of fetal globin genes in adults, and is a potential therapeutic target for the treatment of β-globinopathies such as β-thalassemia and sickle cell disease. The enhancer of
BCL11A
is subject to common genetic variation associated with fetal hemoglobin level. Here, Daniel Bauer and colleagues use a CRISPR–Cas9 approach to perform saturation mutagenesis of the human and mouse
BCL11A
enhancers, producing a map that reveals critical regions and specific vulnerabilities. They validate
BCL11A
enhancer disruption by CRISPR–Cas9 as a therapeutic strategy for inducing fetal haemoglobin by applying it in both mice and primary human erythroblast cells. |
|---|---|
| AbstractList | Enhancers, critical determinants of cellular identity, are commonly identified by correlative chromatin marks and gain-of-function potential, though only loss-of-function studies can demonstrate their requirement in the native genomic context. Previously we identified an erythroid enhancer of
BCL11A
, subject to common genetic variation associated with fetal hemoglobin (HbF) level, whose mouse ortholog is necessary for erythroid BCL11A expression. Here we develop pooled CRISPR-Cas9 guide RNA libraries to perform
in situ
saturating mutagenesis of the human and mouse enhancers. This approach reveals critical minimal features and discrete vulnerabilities of these enhancers. Despite conserved function of the composite enhancers, their architecture diverges. The crucial human sequences appear primate-specific. Through editing of primary human progenitors and mouse transgenesis, we validate the BCL11A erythroid enhancer as a target for HbF reinduction. The detailed enhancer map will inform therapeutic genome editing. The screening approach described here is generally applicable to functional interrogation of noncoding genomic elements. Enhancers, critical determinants of cellular identity, are commonly recognized by correlative chromatin marks and gain-of-function potential, although only loss-of-function studies can demonstrate their requirement in the native genomic context. Previously, we identified an erythroid enhancer of human BCL11A, subject to common genetic variation associated with the fetal haemoglobin level, the mouse orthologue of which is necessary for erythroid BCL11A expression. Here we develop pooled clustered regularly interspaced palindromic repeat (CRISPR)-Cas9 guide RNA libraries to perform in situ saturating mutagenesis of the human and mouse enhancers. This approach reveals critical minimal features and discrete vulnerabilities of these enhancers. Despite conserved function of the composite enhancers, their architecture diverges. The crucial human sequences appear to be primate-specific. Through editing of primary human progenitors and mouse transgenesis, we validate the BCL11A erythroid enhancer as a target for fetal haemoglobin reinduction. The detailed enhancer map will inform therapeutic genome editing, and the screening approach described here is generally applicable to functional interrogation of non-coding genomic elements.Enhancers, critical determinants of cellular identity, are commonly recognized by correlative chromatin marks and gain-of-function potential, although only loss-of-function studies can demonstrate their requirement in the native genomic context. Previously, we identified an erythroid enhancer of human BCL11A, subject to common genetic variation associated with the fetal haemoglobin level, the mouse orthologue of which is necessary for erythroid BCL11A expression. Here we develop pooled clustered regularly interspaced palindromic repeat (CRISPR)-Cas9 guide RNA libraries to perform in situ saturating mutagenesis of the human and mouse enhancers. This approach reveals critical minimal features and discrete vulnerabilities of these enhancers. Despite conserved function of the composite enhancers, their architecture diverges. The crucial human sequences appear to be primate-specific. Through editing of primary human progenitors and mouse transgenesis, we validate the BCL11A erythroid enhancer as a target for fetal haemoglobin reinduction. The detailed enhancer map will inform therapeutic genome editing, and the screening approach described here is generally applicable to functional interrogation of non-coding genomic elements. Enhancers, critical determinants of cellular identity, are commonly recognized by correlative chromatin marks and gain-of-function potential, although only loss-of-function studies can demonstrate their requirement in the native genomic context. Previously, we identified an erythroid enhancer of human BCL11A, subject to common genetic variation associated with the fetal haemoglobin level, the mouse orthologue of which is necessary for erythroid BCL11A expression. Here we develop pooled clustered regularly interspaced palindromic repeat (CRISPR)-Cas9 guide RNA libraries to perform in situ saturating mutagenesis of the human and mouse enhancers. This approach reveals critical minimal features and discrete vulnerabilities of these enhancers. Despite conserved function of the composite enhancers, their architecture diverges. The crucial human sequences appear to be primate-specific. Through editing of primary human progenitors and mouse transgenesis, we validate the BCL11A erythroid enhancer as a target for fetal haemoglobin reinduction. The detailed enhancer map will inform therapeutic genome editing, and the screening approach described here is generally applicable to functional interrogation of non-coding genomic elements. Enhancers, critical determinants of cellular identity, are commonly recognized by correlative chromatin marks and gain-of-function potential, although only loss-of-function studies can demonstrate their requirement in the native genomic context. Previously, we identified an erythroid enhancer of human BCL11A , subject to common genetic variation associated with the fetal haemoglobin level, the mouse orthologue of which is necessary for erythroid BCL11A expression. Here we develop pooled clustered regularly interspaced palindromic repeat (CRISPR)-Cas9 guide RNA libraries to perform in situ saturating mutagenesis of the human and mouse enhancers. This approach reveals critical minimal features and discrete vulnerabilities of these enhancers. Despite conserved function of the composite enhancers, their architecture diverges. The crucial human sequences appear to be primate-specific. Through editing of primary human progenitors and mouse transgenesis, we validate the BCL11A erythroid enhancer as a target for fetal haemoglobin reinduction. The detailed enhancer map will inform therapeutic genome editing, and the screening approach described here is generally applicable to functional interrogation of non-coding genomic elements. A CRISPR-Cas9 approach is used to perform saturating mutagenesis of the human and mouse BCL11A enhancers, producing a map that reveals critical regions and specific vulnerabilities; BCL11A enhancer disruption is validated by CRISPR-Cas9 as a therapeutic strategy for inducing fetal haemoglobin by applying it in both mice and primary human erythroblast cells. BCL11A enhancer disruption analysed BCL11A is a transcriptional repressor that inhibits expression of fetal globin genes in adults, and is a potential therapeutic target for the treatment of β-globinopathies such as β-thalassemia and sickle cell disease. The enhancer of BCL11A is subject to common genetic variation associated with fetal hemoglobin level. Here, Daniel Bauer and colleagues use a CRISPR–Cas9 approach to perform saturation mutagenesis of the human and mouse BCL11A enhancers, producing a map that reveals critical regions and specific vulnerabilities. They validate BCL11A enhancer disruption by CRISPR–Cas9 as a therapeutic strategy for inducing fetal haemoglobin by applying it in both mice and primary human erythroblast cells. |
| Audience | Academic |
| Author | Pinello, Luca Fujiwara, Yuko Vinjamur, Divya S. Luc, Sidinh Sanjana, Neville E. Yuan, Guo-Cheng Shalem, Ophir Sher, Falak Maeda, Takahiro Bauer, Daniel E. Smith, Elenoe C. Chen, Diane D. Schupp, Patrick G. Orkin, Stuart H. Kurita, Ryo Nakamura, Yukio Canver, Matthew C. Garcia, Sara P. Zhang, Feng |
| Author_xml | – sequence: 1 givenname: Matthew C. surname: Canver fullname: Canver, Matthew C. organization: Division of Hematology/Oncology, Department of Pediatric Oncology, Department of Pediatrics, Boston Children’s Hospital, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School – sequence: 2 givenname: Elenoe C. surname: Smith fullname: Smith, Elenoe C. organization: Division of Hematology/Oncology, Department of Pediatric Oncology, Department of Pediatrics, Boston Children’s Hospital, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School – sequence: 3 givenname: Falak surname: Sher fullname: Sher, Falak organization: Division of Hematology/Oncology, Department of Pediatric Oncology, Department of Pediatrics, Boston Children’s Hospital, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School – sequence: 4 givenname: Luca surname: Pinello fullname: Pinello, Luca organization: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health – sequence: 5 givenname: Neville E. surname: Sanjana fullname: Sanjana, Neville E. organization: Department of Brain and Cognitive Sciences and Department of Biological Engineering, Broad Institute of MIT and Harvard, McGovern Institute for Brain Research, MIT – sequence: 6 givenname: Ophir surname: Shalem fullname: Shalem, Ophir organization: Department of Brain and Cognitive Sciences and Department of Biological Engineering, Broad Institute of MIT and Harvard, McGovern Institute for Brain Research, MIT – sequence: 7 givenname: Diane D. surname: Chen fullname: Chen, Diane D. organization: Division of Hematology/Oncology, Department of Pediatric Oncology, Department of Pediatrics, Boston Children’s Hospital, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School – sequence: 8 givenname: Patrick G. surname: Schupp fullname: Schupp, Patrick G. organization: Division of Hematology/Oncology, Department of Pediatric Oncology, Department of Pediatrics, Boston Children’s Hospital, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School – sequence: 9 givenname: Divya S. surname: Vinjamur fullname: Vinjamur, Divya S. organization: Division of Hematology/Oncology, Department of Pediatric Oncology, Department of Pediatrics, Boston Children’s Hospital, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School – sequence: 10 givenname: Sara P. surname: Garcia fullname: Garcia, Sara P. organization: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health – sequence: 11 givenname: Sidinh surname: Luc fullname: Luc, Sidinh organization: Division of Hematology/Oncology, Department of Pediatric Oncology, Department of Pediatrics, Boston Children’s Hospital, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School – sequence: 12 givenname: Ryo surname: Kurita fullname: Kurita, Ryo organization: Cell Engineering Division, RIKEN BioResource Center – sequence: 13 givenname: Yukio surname: Nakamura fullname: Nakamura, Yukio organization: Cell Engineering Division, RIKEN BioResource Center, Comprehensive Human Sciences, University of Tsukuba – sequence: 14 givenname: Yuko surname: Fujiwara fullname: Fujiwara, Yuko organization: Division of Hematology/Oncology, Department of Pediatric Oncology, Department of Pediatrics, Boston Children’s Hospital, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Howard Hughes Medical Institute – sequence: 15 givenname: Takahiro surname: Maeda fullname: Maeda, Takahiro organization: Division of Hematology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School – sequence: 16 givenname: Guo-Cheng surname: Yuan fullname: Yuan, Guo-Cheng organization: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health – sequence: 17 givenname: Feng surname: Zhang fullname: Zhang, Feng email: zhang@broadinstitute.org organization: Department of Brain and Cognitive Sciences and Department of Biological Engineering, Broad Institute of MIT and Harvard, McGovern Institute for Brain Research, MIT – sequence: 18 givenname: Stuart H. surname: Orkin fullname: Orkin, Stuart H. email: stuart_orkin@dfci.harvard.edu organization: Division of Hematology/Oncology, Department of Pediatric Oncology, Department of Pediatrics, Boston Children’s Hospital, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School, Howard Hughes Medical Institute – sequence: 19 givenname: Daniel E. surname: Bauer fullname: Bauer, Daniel E. email: daniel.bauer@childrens.harvard.edu organization: Division of Hematology/Oncology, Department of Pediatric Oncology, Department of Pediatrics, Boston Children’s Hospital, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Harvard Medical School |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26375006$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1038/nature12787 10.1016/j.cell.2013.08.021 10.1126/science.1259037 10.1186/s13072-015-0009-5 10.1126/science.1245813 10.1182/blood-2011-06-362038 10.1073/pnas.1317023110 10.1371/journal.pgen.1002139 10.1038/nature08243 10.1126/science.1211053 10.1038/nbt.2136 10.1126/science.1242088 10.1016/j.cell.2015.01.006 10.1172/JCI61623 10.1126/science.1246981 10.1093/bioinformatics/btr064 10.1038/nature11232 10.1016/j.devcel.2012.09.003 10.1126/science.1222794 10.1038/ng0910-734 10.1038/nmeth.2681 10.1093/nar/gku936 10.1016/0092-8674(81)90413-X 10.1182/blood-2015-04-638528 10.1038/nbt.3026 10.1016/j.cell.2014.02.019 10.1182/blood-2012-06-292078 10.1093/nar/gkt997 10.1038/mt.2008.6 10.1038/nature14299 10.1016/j.stem.2014.10.004 10.1038/nmeth.3047 10.1038/nbt.2647 10.1038/nature07730 10.1038/nbt.2137 10.1074/jbc.M114.564625 10.1126/science.1165409 10.1126/science.1231143 10.1038/nature09906 10.1126/science.1232033 10.1242/dev.072850 10.1016/j.cell.2015.02.040 10.1016/j.molcel.2011.12.021 10.1038/nature13695 10.1038/nature07829 10.1038/nature05295 10.1038/nbt.2800 10.1038/nature14592 10.1172/JCI81163 10.1016/j.cell.2015.02.038 10.1038/nature13166 10.1126/science.1247005 10.1126/science.1246426 10.1073/pnas.1016071107 10.1371/journal.pone.0059890 10.1016/j.cell.2013.03.035 10.1016/S1097-2765(00)80433-5 10.1084/jem.20121846 10.1038/ni925 10.1182/blood.V90.11.4602 |
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| References | Whyte (CR10) 2013; 153 Banerji, Rusconi, Schaffner (CR1) 1981; 27 Mali (CR23) 2013; 339 Shalem (CR25) 2014; 343 Gröschel (CR29) 2014; 157 Brinkman, Chen, Amendola, van Steensel (CR54) 2014; 42 Andersson (CR4) 2014; 507 Ran (CR38) 2013; 154 Hsu (CR39) 2013; 31 Paul (CR11) 2011; 7 Findlay, Boyle, Hause, Klein, Shendure (CR47) 2014; 513 Sexton, Cavalli (CR19) 2015; 160 Koike-Yusa, Li, Tan, Velasco-Herrera, Yusa (CR26) 2014; 32 Patwardhan (CR18) 2012; 30 Visel (CR2) 2009; 457 Weber, Bartsch, Stocking, Fehse (CR59) 2008; 16 Zhou (CR27) 2014; 509 Esvelt (CR46) 2013; 10 Maurano (CR12) 2012; 337 Sanjana, Shalem, Zhang (CR51) 2014; 11 Liu (CR40) 2003; 4 Porcu (CR43) 1997; 90 Kurita (CR34) 2013; 8 Vierstra (CR14) 2014; 346 Wang, Wei, Sabatini, Lander (CR24) 2014; 343 Hardison (CR13) 2010; 42 Xu (CR33) 2011; 334 Hardison, Blobel (CR35) 2013; 342 Ernst (CR8) 2011; 473 Mandal (CR37) 2014; 15 John (CR41) 2012; 139 Yu (CR42) 2012; 209 Ran (CR44) 2015; 520 Giarratana (CR53) 2011; 118 Doench (CR60) 2014; 32 Bauer (CR28) 2013; 342 Dogan (CR56) 2015; 8 Creyghton (CR6) 2010; 107 Johnson (CR21) 2012; 122 Sankaran (CR32) 2009; 460 Villar (CR15) 2015; 160 Bauer, Kamran, Orkin (CR48) 2012; 120 Cong (CR22) 2013; 339 Canver (CR36) 2014; 289 Kowalczyk (CR55) 2012; 45 Basak (CR49) 2015; 125 Melnikov (CR17) 2012; 30 Bender, Bulger, Close, Groudine (CR20) 2000; 5 Chen (CR52) 2015; 160 Thurman (CR3) 2012; 488 Mansour (CR30) 2014; 346 Pennacchio (CR16) 2006; 444 Sankaran (CR31) 2008; 322 Parker (CR9) 2013; 110 Xu (CR7) 2012; 23 Kleinstiver (CR45) 2015; 523 Heintzman (CR5) 2009; 459 Mathelier (CR58) 2014; 42 Funnell (CR50) 2015; 126 Grant, Bailey, Noble (CR57) 2011; 27 T Sexton (BFnature15521_CR19) 2015; 160 J Xu (BFnature15521_CR33) 2011; 334 K Weber (BFnature15521_CR59) 2008; 16 MS Kowalczyk (BFnature15521_CR55) 2012; 45 S Chen (BFnature15521_CR52) 2015; 160 A Melnikov (BFnature15521_CR17) 2012; 30 A Mathelier (BFnature15521_CR58) 2014; 42 L Cong (BFnature15521_CR22) 2013; 339 JG Doench (BFnature15521_CR60) 2014; 32 VG Sankaran (BFnature15521_CR32) 2009; 460 Y Zhou (BFnature15521_CR27) 2014; 509 M Bender (BFnature15521_CR20) 2000; 5 ND Heintzman (BFnature15521_CR5) 2009; 459 R Andersson (BFnature15521_CR4) 2014; 507 KD Johnson (BFnature15521_CR21) 2012; 122 SCJ Parker (BFnature15521_CR9) 2013; 110 Y Yu (BFnature15521_CR42) 2012; 209 MR Mansour (BFnature15521_CR30) 2014; 346 A Basak (BFnature15521_CR49) 2015; 125 RC Hardison (BFnature15521_CR13) 2010; 42 RP Patwardhan (BFnature15521_CR18) 2012; 30 RC Hardison (BFnature15521_CR35) 2013; 342 MT Maurano (BFnature15521_CR12) 2012; 337 DE Bauer (BFnature15521_CR28) 2013; 342 A Visel (BFnature15521_CR2) 2009; 457 D Villar (BFnature15521_CR15) 2015; 160 J Ernst (BFnature15521_CR8) 2011; 473 DE Bauer (BFnature15521_CR48) 2012; 120 LA Pennacchio (BFnature15521_CR16) 2006; 444 S Gröschel (BFnature15521_CR29) 2014; 157 PD Hsu (BFnature15521_CR39) 2013; 31 CE Grant (BFnature15521_CR57) 2011; 27 A John (BFnature15521_CR41) 2012; 139 RE Thurman (BFnature15521_CR3) 2012; 488 N Dogan (BFnature15521_CR56) 2015; 8 P Mali (BFnature15521_CR23) 2013; 339 WA Whyte (BFnature15521_CR10) 2013; 153 GM Findlay (BFnature15521_CR47) 2014; 513 H Koike-Yusa (BFnature15521_CR26) 2014; 32 PW Funnell (BFnature15521_CR50) 2015; 126 J Banerji (BFnature15521_CR1) 1981; 27 EK Brinkman (BFnature15521_CR54) 2014; 42 J Vierstra (BFnature15521_CR14) 2014; 346 NE Sanjana (BFnature15521_CR51) 2014; 11 BP Kleinstiver (BFnature15521_CR45) 2015; 523 T Wang (BFnature15521_CR24) 2014; 343 R Kurita (BFnature15521_CR34) 2013; 8 P Liu (BFnature15521_CR40) 2003; 4 MP Creyghton (BFnature15521_CR6) 2010; 107 FA Ran (BFnature15521_CR38) 2013; 154 O Shalem (BFnature15521_CR25) 2014; 343 MC Canver (BFnature15521_CR36) 2014; 289 KM Esvelt (BFnature15521_CR46) 2013; 10 J Xu (BFnature15521_CR7) 2012; 23 BS Porcu (BFnature15521_CR43) 1997; 90 DS Paul (BFnature15521_CR11) 2011; 7 M Giarratana (BFnature15521_CR53) 2011; 118 PK Mandal (BFnature15521_CR37) 2014; 15 VG Sankaran (BFnature15521_CR31) 2008; 322 FA Ran (BFnature15521_CR44) 2015; 520 |
| References_xml | – volume: 507 start-page: 455 year: 2014 end-page: 461 ident: CR4 article-title: An atlas of active enhancers across human cell types and tissues publication-title: Nature doi: 10.1038/nature12787 – volume: 154 start-page: 1380 year: 2013 end-page: 1389 ident: CR38 article-title: Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity publication-title: Cell doi: 10.1016/j.cell.2013.08.021 – volume: 346 start-page: 1373 year: 2014 end-page: 1377 ident: CR30 article-title: An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element publication-title: Science doi: 10.1126/science.1259037 – volume: 90 start-page: 4602 year: 1997 end-page: 4609 ident: CR43 article-title: The human β globin locus introduced by YAC transfer exhibits a specific and reproducible pattern of developmental regulation in transgenic mice publication-title: Blood – volume: 8 start-page: 16 year: 2015 ident: CR56 article-title: Occupancy by key transcription factors is a more accurate predictor of enhancer activity than histone modifications or chromatin accessibility publication-title: Epigenetics Chromatin doi: 10.1186/s13072-015-0009-5 – volume: 342 start-page: 206 year: 2013 end-page: 207 ident: CR35 article-title: GWAS to therapy by genome edits? publication-title: Science doi: 10.1126/science.1245813 – volume: 118 start-page: 5071 year: 2011 end-page: 5079 ident: CR53 article-title: Proof of principle for transfusion of generated red blood cells publication-title: Blood doi: 10.1182/blood-2011-06-362038 – volume: 110 start-page: 17921 year: 2013 end-page: 17926 ident: CR9 article-title: Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1317023110 – volume: 7 start-page: e1002139 year: 2011 ident: CR11 article-title: Maps of open chromatin guide the functional follow-up of genome-wide association signals: Application to hematological traits publication-title: PLoS Genet. doi: 10.1371/journal.pgen.1002139 – volume: 460 start-page: 1093 year: 2009 end-page: 1097 ident: CR32 article-title: Developmental and species-divergent globin switching are driven by BCL11A publication-title: Nature doi: 10.1038/nature08243 – volume: 334 start-page: 993 year: 2011 end-page: 996 ident: CR33 article-title: Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing publication-title: Science doi: 10.1126/science.1211053 – volume: 30 start-page: 265 year: 2012 end-page: 270 ident: CR18 article-title: Massively parallel functional dissection of mammalian enhancers publication-title: Nature Biotechnol. doi: 10.1038/nbt.2136 – volume: 342 start-page: 253 year: 2013 end-page: 257 ident: CR28 article-title: An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level publication-title: Science doi: 10.1126/science.1242088 – volume: 160 start-page: 554 year: 2015 end-page: 566 ident: CR15 article-title: Enhancer evolution across 20 mammalian species publication-title: Cell doi: 10.1016/j.cell.2015.01.006 – volume: 122 start-page: 3692 year: 2012 end-page: 3704 ident: CR21 article-title: Cis-element mutated in GATA2-dependent immunodeficiency governs hematopoiesis and vascular integrity publication-title: J. Clin. Invest. doi: 10.1172/JCI61623 – volume: 343 start-page: 80 year: 2014 end-page: 84 ident: CR24 article-title: Genetic screens in human cells using the CRISPR-Cas9 system publication-title: Science doi: 10.1126/science.1246981 – volume: 27 start-page: 1017 year: 2011 end-page: 1018 ident: CR57 article-title: FIMO: scanning for occurrences of a given motif publication-title: Bioinformatics doi: 10.1093/bioinformatics/btr064 – volume: 488 start-page: 75 year: 2012 end-page: 82 ident: CR3 article-title: The accessible chromatin landscape of the human genome publication-title: Nature doi: 10.1038/nature11232 – volume: 23 start-page: 796 year: 2012 end-page: 811 ident: CR7 article-title: Combinatorial assembly of developmental stage-specific enhancers controls gene expression programs during human erythropoiesis publication-title: Dev. Cell doi: 10.1016/j.devcel.2012.09.003 – volume: 337 start-page: 1190 year: 2012 end-page: 1195 ident: CR12 article-title: Systematic localization of common disease-associated variation in regulatory DNA publication-title: Science doi: 10.1126/science.1222794 – volume: 42 start-page: 734 year: 2010 end-page: 735 ident: CR13 article-title: Variable evolutionary signatures at the heart of enhancers publication-title: Nature Genet. doi: 10.1038/ng0910-734 – volume: 10 start-page: 1116 year: 2013 end-page: 1121 ident: CR46 article-title: Orthogonal Cas9 proteins for RNA-guided gene regulation and editing publication-title: Nature Methods doi: 10.1038/nmeth.2681 – volume: 42 start-page: e168 year: 2014 ident: CR54 article-title: Easy quantitative assessment of genome editing by sequence trace decomposition publication-title: Nucleic Acids Res. doi: 10.1093/nar/gku936 – volume: 27 start-page: 299 year: 1981 end-page: 308 ident: CR1 article-title: Expression of a β-globin gene is enhanced by remote SV40 DNA sequences publication-title: Cell doi: 10.1016/0092-8674(81)90413-X – volume: 126 start-page: 89 year: 2015 end-page: 93 ident: CR50 article-title: 2p15-p16.1 microdeletions encompassing and proximal to BCL11A are associated with elevated HbF in addition to neurologic impairment publication-title: Blood doi: 10.1182/blood-2015-04-638528 – volume: 32 start-page: 1262 year: 2014 end-page: 1267 ident: CR60 article-title: Rational design of highly active sgRNAs for CRISPR-Cas9-mediated gene inactivation publication-title: Nature Biotechnol. doi: 10.1038/nbt.3026 – volume: 157 start-page: 369 year: 2014 end-page: 381 ident: CR29 article-title: A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in Leukemia publication-title: Cell doi: 10.1016/j.cell.2014.02.019 – volume: 120 start-page: 2945 year: 2012 end-page: 2953 ident: CR48 article-title: Reawakening fetal hemoglobin: Prospects for new therapies for the beta-globin disorders publication-title: Blood doi: 10.1182/blood-2012-06-292078 – volume: 42 start-page: 142 year: 2014 end-page: 147 ident: CR58 article-title: JASPAR 2014: An extensively expanded and updated open-access database of transcription factor binding profiles publication-title: Nucleic Acids Res. doi: 10.1093/nar/gkt997 – volume: 16 start-page: 698 year: 2008 end-page: 706 ident: CR59 article-title: A multicolor panel of novel lentiviral ‘gene ontology’ (LeGO) vectors for functional gene analysis publication-title: Mol. Ther. doi: 10.1038/mt.2008.6 – volume: 520 start-page: 186 year: 2015 end-page: 191 ident: CR44 article-title: genome editing using Cas9 publication-title: Nature doi: 10.1038/nature14299 – volume: 15 start-page: 643 year: 2014 end-page: 652 ident: CR37 article-title: Efficient ablation of genes in human hematopoietic stem and effector cells using CRISPR/Cas9 publication-title: Cell Stem Cell doi: 10.1016/j.stem.2014.10.004 – volume: 11 start-page: 783 year: 2014 end-page: 784 ident: CR51 article-title: Improved vectors and genome-wide libraries for CRISPR screening publication-title: Nature Methods doi: 10.1038/nmeth.3047 – volume: 31 start-page: 827 year: 2013 end-page: 832 ident: CR39 article-title: DNA targeting specificity of RNA-guided Cas9 nucleases publication-title: Nature Biotechnol. doi: 10.1038/nbt.2647 – volume: 457 start-page: 854 year: 2009 end-page: 858 ident: CR2 article-title: ChIP-seq accurately predicts tissue-specific activity of enhancers publication-title: Nature doi: 10.1038/nature07730 – volume: 30 start-page: 271 year: 2012 end-page: 277 ident: CR17 article-title: Systematic dissection and optimization of inducible enhancers in human cells using a massively parallel reporter assay publication-title: Nature Biotechnol. doi: 10.1038/nbt.2137 – volume: 289 start-page: 21312 year: 2014 end-page: 21324 ident: CR36 article-title: Characterization of genomic deletion efficiency mediated by clusted regularly interspaced palindromic repeats (CRISPR)/Cas9 nuclease system in mammalian cells publication-title: J. Biol. Chem. doi: 10.1074/jbc.M114.564625 – volume: 322 start-page: 1839 year: 2008 end-page: 1842 ident: CR31 article-title: Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A publication-title: Science doi: 10.1126/science.1165409 – volume: 339 start-page: 819 year: 2013 end-page: 823 ident: CR22 article-title: Multiplex genome engineering using CRISPR/Cas systems publication-title: Science doi: 10.1126/science.1231143 – volume: 473 start-page: 43 year: 2011 end-page: 49 ident: CR8 article-title: Mapping and analysis of chromatin state dynamics in nine human cell types publication-title: Nature doi: 10.1038/nature09906 – volume: 339 start-page: 823 year: 2013 end-page: 826 ident: CR23 article-title: RNA-guided human genome engineering via Cas9 publication-title: Science doi: 10.1126/science.1232033 – volume: 139 start-page: 1831 year: 2012 end-page: 1841 ident: CR41 article-title: Bcl11a is required for neuronal morphogenesis and sensory circuit formation in dorsal spinal cord development publication-title: Development doi: 10.1242/dev.072850 – volume: 160 start-page: 1049 year: 2015 end-page: 1059 ident: CR19 article-title: The role of chromosome domains in shaping the functional genome publication-title: Cell doi: 10.1016/j.cell.2015.02.040 – volume: 45 start-page: 447 year: 2012 end-page: 458 ident: CR55 article-title: Intragenic enhancers act as alternative promoters publication-title: Mol. Cell doi: 10.1016/j.molcel.2011.12.021 – volume: 513 start-page: 120 year: 2014 end-page: 123 ident: CR47 article-title: Saturation editing of genomic regions by multiplex homology-directed repair publication-title: Nature doi: 10.1038/nature13695 – volume: 459 start-page: 108 year: 2009 end-page: 112 ident: CR5 article-title: Histone modifications at human enhancers reflect global cell-type-specific gene expression publication-title: Nature doi: 10.1038/nature07829 – volume: 444 start-page: 499 year: 2006 end-page: 502 ident: CR16 article-title: enhancer analysis of human conserved non-coding sequences publication-title: Nature doi: 10.1038/nature05295 – volume: 32 start-page: 267 year: 2014 end-page: 273 ident: CR26 article-title: Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library publication-title: Nature Biotechnol. doi: 10.1038/nbt.2800 – volume: 523 start-page: 481 year: 2015 end-page: 485 ident: CR45 article-title: Engineered CRISPR-Cas9 nucleases with altered and improved PAM specificities publication-title: Nature doi: 10.1038/nature14592 – volume: 125 start-page: 2363 year: 2015 end-page: 2368 ident: CR49 article-title: Persistence of fetal hemoglobin and altered neurodevelopment due to BCL11A deletions publication-title: JCI doi: 10.1172/JCI81163 – volume: 160 start-page: 1246 year: 2015 end-page: 1260 ident: CR52 article-title: Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis publication-title: Cell doi: 10.1016/j.cell.2015.02.038 – volume: 509 start-page: 487 year: 2014 end-page: 491 ident: CR27 article-title: High-throughput screening of a CRISPR/Cas9 library for functional genomics in human cells publication-title: Nature doi: 10.1038/nature13166 – volume: 343 start-page: 84 year: 2014 end-page: 87 ident: CR25 article-title: Genome-scale CRISPR-Cas9 knockout screening in human cells publication-title: Science doi: 10.1126/science.1247005 – volume: 346 start-page: 1007 year: 2014 end-page: 1012 ident: CR14 article-title: Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution publication-title: Science doi: 10.1126/science.1246426 – volume: 107 start-page: 21931 year: 2010 end-page: 21936 ident: CR6 article-title: Histone H3K27ac separates active from poised enhancers and predicts developmental state publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1016071107 – volume: 8 start-page: e59890 year: 2013 ident: CR34 article-title: Establishment of immortalized human erythroid progenitor cell lines able to produce enucleated red blood cells publication-title: PLoS ONE doi: 10.1371/journal.pone.0059890 – volume: 153 start-page: 307 year: 2013 end-page: 319 ident: CR10 article-title: Master transcription factors and mediator establish super-enhancers at key cell identity genes publication-title: Cell doi: 10.1016/j.cell.2013.03.035 – volume: 5 start-page: 387 year: 2000 end-page: 393 ident: CR20 article-title: β-globin gene switching and DNase I sensitivity of the endogenous β-globin locus in mice do not require the locus control region publication-title: Mol. Cell doi: 10.1016/S1097-2765(00)80433-5 – volume: 209 start-page: 2467 year: 2012 end-page: 2483 ident: CR42 article-title: Bcl11a is essential for lymphoid development and negatively regulates p53 publication-title: J. Exp. Med. doi: 10.1084/jem.20121846 – volume: 4 start-page: 525 year: 2003 end-page: 532 ident: CR40 article-title: Bcl11a is essential for normal lymphoid development publication-title: Nature Immunol. doi: 10.1038/ni925 – volume: 343 start-page: 80 year: 2014 ident: BFnature15521_CR24 publication-title: Science doi: 10.1126/science.1246981 – volume: 154 start-page: 1380 year: 2013 ident: BFnature15521_CR38 publication-title: Cell doi: 10.1016/j.cell.2013.08.021 – volume: 32 start-page: 1262 year: 2014 ident: BFnature15521_CR60 publication-title: Nature Biotechnol. doi: 10.1038/nbt.3026 – volume: 209 start-page: 2467 year: 2012 ident: BFnature15521_CR42 publication-title: J. Exp. Med. doi: 10.1084/jem.20121846 – volume: 120 start-page: 2945 year: 2012 ident: BFnature15521_CR48 publication-title: Blood doi: 10.1182/blood-2012-06-292078 – volume: 139 start-page: 1831 year: 2012 ident: BFnature15521_CR41 publication-title: Development doi: 10.1242/dev.072850 – volume: 473 start-page: 43 year: 2011 ident: BFnature15521_CR8 publication-title: Nature doi: 10.1038/nature09906 – volume: 90 start-page: 4602 year: 1997 ident: BFnature15521_CR43 publication-title: Blood doi: 10.1182/blood.V90.11.4602 – volume: 337 start-page: 1190 year: 2012 ident: BFnature15521_CR12 publication-title: Science doi: 10.1126/science.1222794 – volume: 457 start-page: 854 year: 2009 ident: BFnature15521_CR2 publication-title: Nature doi: 10.1038/nature07730 – volume: 509 start-page: 487 year: 2014 ident: BFnature15521_CR27 publication-title: Nature doi: 10.1038/nature13166 – volume: 513 start-page: 120 year: 2014 ident: BFnature15521_CR47 publication-title: Nature doi: 10.1038/nature13695 – volume: 342 start-page: 206 year: 2013 ident: BFnature15521_CR35 publication-title: Science doi: 10.1126/science.1245813 – volume: 488 start-page: 75 year: 2012 ident: BFnature15521_CR3 publication-title: Nature doi: 10.1038/nature11232 – volume: 32 start-page: 267 year: 2014 ident: BFnature15521_CR26 publication-title: Nature Biotechnol. doi: 10.1038/nbt.2800 – volume: 342 start-page: 253 year: 2013 ident: BFnature15521_CR28 publication-title: Science doi: 10.1126/science.1242088 – volume: 339 start-page: 823 year: 2013 ident: BFnature15521_CR23 publication-title: Science doi: 10.1126/science.1232033 – volume: 42 start-page: 142 year: 2014 ident: BFnature15521_CR58 publication-title: Nucleic Acids Res. doi: 10.1093/nar/gkt997 – volume: 444 start-page: 499 year: 2006 ident: BFnature15521_CR16 publication-title: Nature doi: 10.1038/nature05295 – volume: 507 start-page: 455 year: 2014 ident: BFnature15521_CR4 publication-title: Nature doi: 10.1038/nature12787 – volume: 42 start-page: 734 year: 2010 ident: BFnature15521_CR13 publication-title: Nature Genet. doi: 10.1038/ng0910-734 – volume: 118 start-page: 5071 year: 2011 ident: BFnature15521_CR53 publication-title: Blood doi: 10.1182/blood-2011-06-362038 – volume: 30 start-page: 265 year: 2012 ident: BFnature15521_CR18 publication-title: Nature Biotechnol. doi: 10.1038/nbt.2136 – volume: 27 start-page: 1017 year: 2011 ident: BFnature15521_CR57 publication-title: Bioinformatics doi: 10.1093/bioinformatics/btr064 – volume: 459 start-page: 108 year: 2009 ident: BFnature15521_CR5 publication-title: Nature doi: 10.1038/nature07829 – volume: 346 start-page: 1007 year: 2014 ident: BFnature15521_CR14 publication-title: Science doi: 10.1126/science.1246426 – volume: 334 start-page: 993 year: 2011 ident: BFnature15521_CR33 publication-title: Science doi: 10.1126/science.1211053 – volume: 107 start-page: 21931 year: 2010 ident: BFnature15521_CR6 publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1016071107 – volume: 11 start-page: 783 year: 2014 ident: BFnature15521_CR51 publication-title: Nature Methods doi: 10.1038/nmeth.3047 – volume: 153 start-page: 307 year: 2013 ident: BFnature15521_CR10 publication-title: Cell doi: 10.1016/j.cell.2013.03.035 – volume: 4 start-page: 525 year: 2003 ident: BFnature15521_CR40 publication-title: Nature Immunol. doi: 10.1038/ni925 – volume: 523 start-page: 481 year: 2015 ident: BFnature15521_CR45 publication-title: Nature doi: 10.1038/nature14592 – volume: 460 start-page: 1093 year: 2009 ident: BFnature15521_CR32 publication-title: Nature doi: 10.1038/nature08243 – volume: 346 start-page: 1373 year: 2014 ident: BFnature15521_CR30 publication-title: Science doi: 10.1126/science.1259037 – volume: 126 start-page: 89 year: 2015 ident: BFnature15521_CR50 publication-title: Blood doi: 10.1182/blood-2015-04-638528 – volume: 160 start-page: 1246 year: 2015 ident: BFnature15521_CR52 publication-title: Cell doi: 10.1016/j.cell.2015.02.038 – volume: 8 start-page: 16 year: 2015 ident: BFnature15521_CR56 publication-title: Epigenetics Chromatin doi: 10.1186/s13072-015-0009-5 – volume: 289 start-page: 21312 year: 2014 ident: BFnature15521_CR36 publication-title: J. Biol. Chem. doi: 10.1074/jbc.M114.564625 – volume: 15 start-page: 643 year: 2014 ident: BFnature15521_CR37 publication-title: Cell Stem Cell doi: 10.1016/j.stem.2014.10.004 – volume: 23 start-page: 796 year: 2012 ident: BFnature15521_CR7 publication-title: Dev. Cell doi: 10.1016/j.devcel.2012.09.003 – volume: 125 start-page: 2363 year: 2015 ident: BFnature15521_CR49 publication-title: JCI doi: 10.1172/JCI81163 – volume: 110 start-page: 17921 year: 2013 ident: BFnature15521_CR9 publication-title: Proc. Natl Acad. Sci. USA doi: 10.1073/pnas.1317023110 – volume: 42 start-page: e168 year: 2014 ident: BFnature15521_CR54 publication-title: Nucleic Acids Res. doi: 10.1093/nar/gku936 – volume: 16 start-page: 698 year: 2008 ident: BFnature15521_CR59 publication-title: Mol. Ther. doi: 10.1038/mt.2008.6 – volume: 31 start-page: 827 year: 2013 ident: BFnature15521_CR39 publication-title: Nature Biotechnol. doi: 10.1038/nbt.2647 – volume: 45 start-page: 447 year: 2012 ident: BFnature15521_CR55 publication-title: Mol. Cell doi: 10.1016/j.molcel.2011.12.021 – volume: 5 start-page: 387 year: 2000 ident: BFnature15521_CR20 publication-title: Mol. Cell doi: 10.1016/S1097-2765(00)80433-5 – volume: 10 start-page: 1116 year: 2013 ident: BFnature15521_CR46 publication-title: Nature Methods doi: 10.1038/nmeth.2681 – volume: 122 start-page: 3692 year: 2012 ident: BFnature15521_CR21 publication-title: J. Clin. Invest. doi: 10.1172/JCI61623 – volume: 27 start-page: 299 year: 1981 ident: BFnature15521_CR1 publication-title: Cell doi: 10.1016/0092-8674(81)90413-X – volume: 7 start-page: e1002139 year: 2011 ident: BFnature15521_CR11 publication-title: PLoS Genet. doi: 10.1371/journal.pgen.1002139 – volume: 160 start-page: 554 year: 2015 ident: BFnature15521_CR15 publication-title: Cell doi: 10.1016/j.cell.2015.01.006 – volume: 160 start-page: 1049 year: 2015 ident: BFnature15521_CR19 publication-title: Cell doi: 10.1016/j.cell.2015.02.040 – volume: 157 start-page: 369 year: 2014 ident: BFnature15521_CR29 publication-title: Cell doi: 10.1016/j.cell.2014.02.019 – volume: 8 start-page: e59890 year: 2013 ident: BFnature15521_CR34 publication-title: PLoS ONE doi: 10.1371/journal.pone.0059890 – volume: 339 start-page: 819 year: 2013 ident: BFnature15521_CR22 publication-title: Science doi: 10.1126/science.1231143 – volume: 30 start-page: 271 year: 2012 ident: BFnature15521_CR17 publication-title: Nature Biotechnol. doi: 10.1038/nbt.2137 – volume: 322 start-page: 1839 year: 2008 ident: BFnature15521_CR31 publication-title: Science doi: 10.1126/science.1165409 – volume: 343 start-page: 84 year: 2014 ident: BFnature15521_CR25 publication-title: Science doi: 10.1126/science.1247005 – volume: 520 start-page: 186 year: 2015 ident: BFnature15521_CR44 publication-title: Nature doi: 10.1038/nature14299 |
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| Title | BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis |
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