Chromatin Accessibility Dynamics during iPSC Reprogramming
Cell-fate decisions remain poorly understood at the chromatin level. Here, we map chromatin remodeling dynamics during induction of pluripotent stem cells. ATAC-seq profiling of MEFs expressing Oct4-Sox2-Klf4 (OSK) reveals dynamic changes in chromatin states shifting from open to closed (OC) and clo...
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| Published in | Cell stem cell Vol. 21; no. 6; pp. 819 - 833.e6 |
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| Main Authors | , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
07.12.2017
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Cell-fate decisions remain poorly understood at the chromatin level. Here, we map chromatin remodeling dynamics during induction of pluripotent stem cells. ATAC-seq profiling of MEFs expressing Oct4-Sox2-Klf4 (OSK) reveals dynamic changes in chromatin states shifting from open to closed (OC) and closed to open (CO), with an initial burst of OC and an ending surge of CO. The OC loci are largely composed of genes associated with a somatic fate, while the CO loci are associated with pluripotency. Factors/conditions known to impede reprogramming prevent OSK-driven OC and skew OC-CO dynamics. While the CO loci are enriched for OSK motifs, the OC loci are not, suggesting alternative mechanisms for chromatin closing. Sap30, a Sin3A corepressor complex component, is required for the OC shift and facilitates reduced H3K27ac deposition at OC loci. These results reveal a chromatin accessibility logic during reprogramming that may apply to other cell-fate decisions.
[Display omitted]
•ATAC-seq reveals chromatin accessibility dynamics during reprogramming•TFs associated with initial chromatin closing are barriers for reprogramming•OSK opens the pluripotent loci gradually through a direct process•OSK closes the somatic loci indirectly in part through SAP30
Li et al. show that Yamanaka factors remodel the nuclear architecture of MEFs following a binary logic that may guide further improvement in reprograming technology and be applicable for other cell-fate decisions. |
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| AbstractList | Cell-fate decisions remain poorly understood at the chromatin level. Here, we map chromatin remodeling dynamics during induction of pluripotent stem cells. ATAC-seq profiling of MEFs expressing Oct4-Sox2-Klf4 (OSK) reveals dynamic changes in chromatin states shifting from open to closed (OC) and closed to open (CO), with an initial burst of OC and an ending surge of CO. The OC loci are largely composed of genes associated with a somatic fate, while the CO loci are associated with pluripotency. Factors/conditions known to impede reprogramming prevent OSK-driven OC and skew OC-CO dynamics. While the CO loci are enriched for OSK motifs, the OC loci are not, suggesting alternative mechanisms for chromatin closing. Sap30, a Sin3A corepressor complex component, is required for the OC shift and facilitates reduced H3K27ac deposition at OC loci. These results reveal a chromatin accessibility logic during reprogramming that may apply to other cell-fate decisions.Cell-fate decisions remain poorly understood at the chromatin level. Here, we map chromatin remodeling dynamics during induction of pluripotent stem cells. ATAC-seq profiling of MEFs expressing Oct4-Sox2-Klf4 (OSK) reveals dynamic changes in chromatin states shifting from open to closed (OC) and closed to open (CO), with an initial burst of OC and an ending surge of CO. The OC loci are largely composed of genes associated with a somatic fate, while the CO loci are associated with pluripotency. Factors/conditions known to impede reprogramming prevent OSK-driven OC and skew OC-CO dynamics. While the CO loci are enriched for OSK motifs, the OC loci are not, suggesting alternative mechanisms for chromatin closing. Sap30, a Sin3A corepressor complex component, is required for the OC shift and facilitates reduced H3K27ac deposition at OC loci. These results reveal a chromatin accessibility logic during reprogramming that may apply to other cell-fate decisions. Cell-fate decisions remain poorly understood at the chromatin level. Here, we map chromatin remodeling dynamics during induction of pluripotent stem cells. ATAC-seq profiling of MEFs expressing Oct4-Sox2-Klf4 (OSK) reveals dynamic changes in chromatin states shifting from open to closed (OC) and closed to open (CO), with an initial burst of OC and an ending surge of CO. The OC loci are largely composed of genes associated with a somatic fate, while the CO loci are associated with pluripotency. Factors/conditions known to impede reprogramming prevent OSK-driven OC and skew OC-CO dynamics. While the CO loci are enriched for OSK motifs, the OC loci are not, suggesting alternative mechanisms for chromatin closing. Sap30, a Sin3A corepressor complex component, is required for the OC shift and facilitates reduced H3K27ac deposition at OC loci. These results reveal a chromatin accessibility logic during reprogramming that may apply to other cell-fate decisions. Cell-fate decisions remain poorly understood at the chromatin level. Here, we map chromatin remodeling dynamics during induction of pluripotent stem cells. ATAC-seq profiling of MEFs expressing Oct4-Sox2-Klf4 (OSK) reveals dynamic changes in chromatin states shifting from open to closed (OC) and closed to open (CO), with an initial burst of OC and an ending surge of CO. The OC loci are largely composed of genes associated with a somatic fate, while the CO loci are associated with pluripotency. Factors/conditions known to impede reprogramming prevent OSK-driven OC and skew OC-CO dynamics. While the CO loci are enriched for OSK motifs, the OC loci are not, suggesting alternative mechanisms for chromatin closing. Sap30, a Sin3A corepressor complex component, is required for the OC shift and facilitates reduced H3K27ac deposition at OC loci. These results reveal a chromatin accessibility logic during reprogramming that may apply to other cell-fate decisions. [Display omitted] •ATAC-seq reveals chromatin accessibility dynamics during reprogramming•TFs associated with initial chromatin closing are barriers for reprogramming•OSK opens the pluripotent loci gradually through a direct process•OSK closes the somatic loci indirectly in part through SAP30 Li et al. show that Yamanaka factors remodel the nuclear architecture of MEFs following a binary logic that may guide further improvement in reprograming technology and be applicable for other cell-fate decisions. |
| Author | Wu, Chuman Qin, Yue Wang, Xiaoshan Yu, Shenyong Liu, He Pei, Duanqing Liu, Jing Kuang, Junqi Guo, Lin Chen, Jiekai Zhou, Chunhua Hutchins, Andrew P. Yang, Xuejie Li, Dongwei He, Jiangping Guo, Jing Wu, Fang |
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Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China – sequence: 5 givenname: Jing surname: Guo fullname: Guo, Jing organization: CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China – sequence: 6 givenname: Chuman surname: Wu fullname: Wu, Chuman organization: CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China – sequence: 7 givenname: Yue surname: Qin fullname: Qin, Yue organization: CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China – sequence: 8 givenname: Lin surname: Guo fullname: Guo, Lin organization: CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China – sequence: 9 givenname: Jiangping surname: He fullname: He, Jiangping organization: CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China – sequence: 10 givenname: Shenyong surname: Yu fullname: Yu, Shenyong organization: CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China – sequence: 11 givenname: He surname: Liu fullname: Liu, He organization: CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China – sequence: 12 givenname: Xiaoshan surname: Wang fullname: Wang, Xiaoshan organization: CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China – sequence: 13 givenname: Fang surname: Wu fullname: Wu, Fang organization: CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China – sequence: 14 givenname: Junqi surname: Kuang fullname: Kuang, Junqi organization: CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China – sequence: 15 givenname: Andrew P. surname: Hutchins fullname: Hutchins, Andrew P. email: aphutchins@icloud.com organization: CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China – sequence: 16 givenname: Jiekai surname: Chen fullname: Chen, Jiekai email: chen_jiekai@gibh.ac.cn organization: CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China – sequence: 17 givenname: Duanqing surname: Pei fullname: Pei, Duanqing email: pei_duanqing@gibh.ac.cn organization: CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China |
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| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Cell stem cell |
| PublicationTitleAlternate | Cell Stem Cell |
| PublicationYear | 2017 |
| Publisher | Elsevier Inc |
| Publisher_xml | – name: Elsevier Inc |
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| Snippet | Cell-fate decisions remain poorly understood at the chromatin level. Here, we map chromatin remodeling dynamics during induction of pluripotent stem cells.... |
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| SubjectTerms | Animals binary logic Cells, Cultured Cellular Reprogramming Chromatin - genetics Chromatin - metabolism chromatin dynamics Induced Pluripotent Stem Cells - cytology Induced Pluripotent Stem Cells - metabolism Kruppel-Like Transcription Factors - metabolism Mice Octamer Transcription Factor-3 - metabolism open/close reprogramming Sap30 SOXB1 Transcription Factors - metabolism |
| Title | Chromatin Accessibility Dynamics during iPSC Reprogramming |
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