Primary effusion lymphoma enhancer connectome links super-enhancers to dependency factors

Primary effusion lymphoma (PEL) has a very poor prognosis. To evaluate the contributions of enhancers/promoters interactions to PEL cell growth and survival, here we produce H3K27ac HiChIP datasets in PEL cells. This allows us to generate the PEL enhancer connectome, which links enhancers and promot...

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Published inNature communications Vol. 11; no. 1; pp. 6318 - 13
Main Authors Wang, Chong, Zhang, Luyao, Ke, Liangru, Ding, Weiyue, Jiang, Sizun, Li, Difei, Narita, Yohei, Hou, Isabella, Liang, Jun, Li, Shijun, Xiao, Haipeng, Gottwein, Eva, Kaye, Kenneth M., Teng, Mingxiang, Zhao, Bo
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 09.12.2020
Nature Publishing Group
Nature Portfolio
Subjects
13/1
13/106
13/109
38/1
38/43
38/61
38/77
38/88
45
45/15
45/22
631/1647/2210/2211
631/337/100/101
631/337/100/102
631/337/176/2016
64
96
Cell growth
Cell Line, Tumor
Cell Proliferation - genetics
Cell survival
Chromatin Immunoprecipitation Sequencing
CRISPR
Dependence
Effusion
Enhancer Elements, Genetic - genetics
Enhancers
Gene expression
Gene Expression Regulation, Neoplastic
Gene Knockout Techniques
Gene Regulatory Networks
Genomes
Herpesvirus 8, Human - pathogenicity
Histones - genetics
Humanities and Social Sciences
Humans
Interferon regulatory factor 4
Interferon Regulatory Factors - genetics
Links
Lymphoma
Lymphoma, Primary Effusion - genetics
Lymphoma, Primary Effusion - pathology
Lymphoma, Primary Effusion - virology
Mcl-1 protein
MDM2 protein
Medical prognosis
MEF2 Transcription Factors - genetics
MEF2 Transcription Factors - metabolism
multidisciplinary
Myc protein
Pathogenesis
Perturbation
Primary effusion lymphoma
Prognosis
Promoter Regions, Genetic - genetics
Promoters
Proto-Oncogene Proteins c-myc - genetics
Repressors
Science
Science (multidisciplinary)
Tethering
Transcription factors
Online AccessGet full text

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Abstract Primary effusion lymphoma (PEL) has a very poor prognosis. To evaluate the contributions of enhancers/promoters interactions to PEL cell growth and survival, here we produce H3K27ac HiChIP datasets in PEL cells. This allows us to generate the PEL enhancer connectome, which links enhancers and promoters in PEL genome-wide. We identify more than 8000 genomic interactions in each PEL cell line. By incorporating HiChIP data with H3K27ac ChIP-seq data, we identify interactions between enhancers/enhancers, enhancers/promoters, and promoters/promoters. HiChIP further links PEL super-enhancers to PEL dependency factors MYC, IRF4, MCL1, CCND2, MDM2, and CFLAR. CRISPR knock out of MEF2C and IRF4 significantly reduces MYC and IRF4 super-enhancer H3K27ac signal. Knock out also reduces MYC and IRF4 expression. CRISPRi perturbation of these super-enhancers by tethering transcription repressors to enhancers significantly reduces target gene expression and reduces PEL cell growth. These data provide insights into PEL molecular pathogenesis. Primary effusion lymphoma (PEL) has a very poor prognosis. Here, the authors perform H3K27ac HiChIP in PEL cells and generate the PEL enhancer connectome, linking enhancers and promoters in PEL, as well as super-enhancers to dependency factors.
AbstractList Primary effusion lymphoma (PEL) has a very poor prognosis. To evaluate the contributions of enhancers/promoters interactions to PEL cell growth and survival, here we produce H3K27ac HiChIP datasets in PEL cells. This allows us to generate the PEL enhancer connectome, which links enhancers and promoters in PEL genome-wide. We identify more than 8000 genomic interactions in each PEL cell line. By incorporating HiChIP data with H3K27ac ChIP-seq data, we identify interactions between enhancers/enhancers, enhancers/promoters, and promoters/promoters. HiChIP further links PEL super-enhancers to PEL dependency factors MYC, IRF4, MCL1, CCND2, MDM2, and CFLAR. CRISPR knock out of MEF2C and IRF4 significantly reduces MYC and IRF4 super-enhancer H3K27ac signal. Knock out also reduces MYC and IRF4 expression. CRISPRi perturbation of these super-enhancers by tethering transcription repressors to enhancers significantly reduces target gene expression and reduces PEL cell growth. These data provide insights into PEL molecular pathogenesis. Primary effusion lymphoma (PEL) has a very poor prognosis. Here, the authors perform H3K27ac HiChIP in PEL cells and generate the PEL enhancer connectome, linking enhancers and promoters in PEL, as well as super-enhancers to dependency factors.
Primary effusion lymphoma (PEL) has a very poor prognosis. To evaluate the contributions of enhancers/promoters interactions to PEL cell growth and survival, here we produce H3K27ac HiChIP datasets in PEL cells. This allows us to generate the PEL enhancer connectome, which links enhancers and promoters in PEL genome-wide. We identify more than 8000 genomic interactions in each PEL cell line. By incorporating HiChIP data with H3K27ac ChIP-seq data, we identify interactions between enhancers/enhancers, enhancers/promoters, and promoters/promoters. HiChIP further links PEL super-enhancers to PEL dependency factors MYC, IRF4, MCL1, CCND2, MDM2, and CFLAR. CRISPR knock out of MEF2C and IRF4 significantly reduces MYC and IRF4 super-enhancer H3K27ac signal. Knock out also reduces MYC and IRF4 expression. CRISPRi perturbation of these super-enhancers by tethering transcription repressors to enhancers significantly reduces target gene expression and reduces PEL cell growth. These data provide insights into PEL molecular pathogenesis.Primary effusion lymphoma (PEL) has a very poor prognosis. Here, the authors perform H3K27ac HiChIP in PEL cells and generate the PEL enhancer connectome, linking enhancers and promoters in PEL, as well as super-enhancers to dependency factors.
Primary effusion lymphoma (PEL) has a very poor prognosis. To evaluate the contributions of enhancers/promoters interactions to PEL cell growth and survival, here we produce H3K27ac HiChIP datasets in PEL cells. This allows us to generate the PEL enhancer connectome, which links enhancers and promoters in PEL genome-wide. We identify more than 8000 genomic interactions in each PEL cell line. By incorporating HiChIP data with H3K27ac ChIP-seq data, we identify interactions between enhancers/enhancers, enhancers/promoters, and promoters/promoters. HiChIP further links PEL super-enhancers to PEL dependency factors MYC, IRF4, MCL1, CCND2, MDM2, and CFLAR. CRISPR knock out of MEF2C and IRF4 significantly reduces MYC and IRF4 super-enhancer H3K27ac signal. Knock out also reduces MYC and IRF4 expression. CRISPRi perturbation of these super-enhancers by tethering transcription repressors to enhancers significantly reduces target gene expression and reduces PEL cell growth. These data provide insights into PEL molecular pathogenesis.
Primary effusion lymphoma (PEL) has a very poor prognosis. Here, the authors perform H3K27ac HiChIP in PEL cells and generate the PEL enhancer connectome, linking enhancers and promoters in PEL, as well as super-enhancers to dependency factors.
Primary effusion lymphoma (PEL) has a very poor prognosis. To evaluate the contributions of enhancers/promoters interactions to PEL cell growth and survival, here we produce H3K27ac HiChIP datasets in PEL cells. This allows us to generate the PEL enhancer connectome, which links enhancers and promoters in PEL genome-wide. We identify more than 8000 genomic interactions in each PEL cell line. By incorporating HiChIP data with H3K27ac ChIP-seq data, we identify interactions between enhancers/enhancers, enhancers/promoters, and promoters/promoters. HiChIP further links PEL super-enhancers to PEL dependency factors MYC, IRF4, MCL1, CCND2, MDM2, and CFLAR. CRISPR knock out of MEF2C and IRF4 significantly reduces MYC and IRF4 super-enhancer H3K27ac signal. Knock out also reduces MYC and IRF4 expression. CRISPRi perturbation of these super-enhancers by tethering transcription repressors to enhancers significantly reduces target gene expression and reduces PEL cell growth. These data provide insights into PEL molecular pathogenesis.Primary effusion lymphoma (PEL) has a very poor prognosis. To evaluate the contributions of enhancers/promoters interactions to PEL cell growth and survival, here we produce H3K27ac HiChIP datasets in PEL cells. This allows us to generate the PEL enhancer connectome, which links enhancers and promoters in PEL genome-wide. We identify more than 8000 genomic interactions in each PEL cell line. By incorporating HiChIP data with H3K27ac ChIP-seq data, we identify interactions between enhancers/enhancers, enhancers/promoters, and promoters/promoters. HiChIP further links PEL super-enhancers to PEL dependency factors MYC, IRF4, MCL1, CCND2, MDM2, and CFLAR. CRISPR knock out of MEF2C and IRF4 significantly reduces MYC and IRF4 super-enhancer H3K27ac signal. Knock out also reduces MYC and IRF4 expression. CRISPRi perturbation of these super-enhancers by tethering transcription repressors to enhancers significantly reduces target gene expression and reduces PEL cell growth. These data provide insights into PEL molecular pathogenesis.
ArticleNumber 6318
Author Ke, Liangru
Jiang, Sizun
Narita, Yohei
Ding, Weiyue
Teng, Mingxiang
Li, Shijun
Gottwein, Eva
Liang, Jun
Zhao, Bo
Wang, Chong
Hou, Isabella
Xiao, Haipeng
Zhang, Luyao
Kaye, Kenneth M.
Li, Difei
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/33298918$$D View this record in MEDLINE/PubMed
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Snippet Primary effusion lymphoma (PEL) has a very poor prognosis. To evaluate the contributions of enhancers/promoters interactions to PEL cell growth and survival,...
Primary effusion lymphoma (PEL) has a very poor prognosis. Here, the authors perform H3K27ac HiChIP in PEL cells and generate the PEL enhancer connectome,...
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SubjectTerms 13/1
13/106
13/109
38/1
38/43
38/61
38/77
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45
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45/22
631/1647/2210/2211
631/337/100/101
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631/337/176/2016
64
96
Cell growth
Cell Line, Tumor
Cell Proliferation - genetics
Cell survival
Chromatin Immunoprecipitation Sequencing
CRISPR
Dependence
Effusion
Enhancer Elements, Genetic - genetics
Enhancers
Gene expression
Gene Expression Regulation, Neoplastic
Gene Knockout Techniques
Gene Regulatory Networks
Genomes
Herpesvirus 8, Human - pathogenicity
Histones - genetics
Humanities and Social Sciences
Humans
Interferon regulatory factor 4
Interferon Regulatory Factors - genetics
Links
Lymphoma
Lymphoma, Primary Effusion - genetics
Lymphoma, Primary Effusion - pathology
Lymphoma, Primary Effusion - virology
Mcl-1 protein
MDM2 protein
Medical prognosis
MEF2 Transcription Factors - genetics
MEF2 Transcription Factors - metabolism
multidisciplinary
Myc protein
Pathogenesis
Perturbation
Primary effusion lymphoma
Prognosis
Promoter Regions, Genetic - genetics
Promoters
Proto-Oncogene Proteins c-myc - genetics
Repressors
Science
Science (multidisciplinary)
Tethering
Transcription factors
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Title Primary effusion lymphoma enhancer connectome links super-enhancers to dependency factors
URI https://link.springer.com/article/10.1038/s41467-020-20136-w
https://www.ncbi.nlm.nih.gov/pubmed/33298918
https://www.proquest.com/docview/2473295109
https://www.proquest.com/docview/2469090580
https://pubmed.ncbi.nlm.nih.gov/PMC7726151
https://doaj.org/article/3b0cb7b6da294c72b4d1187e13551c79
Volume 11
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