Discovery of Competent Chromatin Regions in Human Embryonic Stem Cells
Pulecio Julian 1Damodaran Jeyaram R 1Murphy Dylan 2Rickert Robert W. 1Apostolou Effie 2Leslie Christina S. 3Huangfu Danwei 1Tayyebi Zakieh 4Zhou Ting 5Luo Renhe 6Wong Wilfred 3Li Wenbo 7Yang Dexin 7Kaplan Samuel 8Shukla Abhijit 1Liu Dingyu 6Zhong Aaron 5Cho Hyunwoo 1Yan Jielin 6Gonz¨￠lez Federico9
作者信息
- 1. Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
- 2. Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medical College||Sanford I Weill department of Medicine, Sandra and Edward Meyer Cancer center, Weill Cornell Medicine
- 3. Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
- 4. Computational and Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center||Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medical College
- 5. The SKI Stem Cell Research Facility, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center
- 6. Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center||Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center
- 7. Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center||Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center and UTHealth
- 8. Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center||Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medical College
- 9. Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center||Genomics for Precision Medicine, Health Research Institute of the Balearic Islands (IdISBa), University Hospital Son Espases (HUSE)
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Abstract
ABSTRACT
The mechanisms underlying the ability of embryonic stem cells (ESCs) to rapidly activate lineage-specific genes during differentiation remain largely unknown. Through multiple CRISPR-activation screens, we discovered human ESCs have pre-established transcriptionally competent chromatin regions (CCRs) that support lineage-specific gene expression at levels comparable to differentiated cells. CCRs reside in the same topological domains as their target genes. They lack typical enhancer-associated histone modifications but show enriched occupancy of pluripotent transcription factors, DNA demethylation factors, and histone deacetylases. TET1 and QSER1 protect CCRs from excessive DNA methylation, while HDAC1 family members prevent premature activation. This “push and pull” feature resembles bivalent domains at developmental gene promoters but involves distinct molecular mechanisms. Our study provides new insights into pluripotency regulation and cellular plasticity in development and disease.
One sentence summaryWe report a class of distal regulatory regions distinct from enhancers that confer human embryonic stem cells with the competence to rapidly activate the expression of lineage-specific genes.引用本文复制引用
Pulecio Julian,Damodaran Jeyaram R,Murphy Dylan,Rickert Robert W.,Apostolou Effie,Leslie Christina S.,Huangfu Danwei,Tayyebi Zakieh,Zhou Ting,Luo Renhe,Wong Wilfred,Li Wenbo,Yang Dexin,Kaplan Samuel,Shukla Abhijit,Liu Dingyu,Zhong Aaron,Cho Hyunwoo,Yan Jielin,Gonz¨￠lez Federico.Discovery of Competent Chromatin Regions in Human Embryonic Stem Cells[EB/OL].(2025-03-28)[2026-04-20].https://www.biorxiv.org/content/10.1101/2023.06.14.544990.学科分类
遗传学/细胞生物学/分子生物学
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