Control of Embryonic Stem Cell Identity by BRD4-Dependent Transcriptional Elongation of Super-Enhancer-Associated Pluripotency Genes

Year: 2014

Type: article

Abstract: Transcription factors and chromatin-remodeling complexes are key determinants of embryonic stem cell (ESC) identity. Here, we demonstrate that BRD4, a member of the bromodomain and extraterminal domain (BET) family of epigenetic readers, regulates the self-renewal ability and pluripotency of ESCs. BRD4 inhibition resulted in induction of epithelial-to-mesenchymal transition (EMT) markers and commitment to the neuroectodermal lineage while reducing the ESC multidifferentiation capacity in teratoma assays. BRD4 maintains transcription of core stem cell genes such as OCT4 and PRDM14 by occupying their super-enhancers (SEs), large clusters of regulatory elements, and recruiting to them Mediator and CDK9, the catalytic subunit of the positive transcription elongation factor b (P-TEFb), to allow Pol-II-dependent productive elongation. Our study describes a mechanism of regulation of ESC identity that could be applied to improve the efficiency of ESC differentiation.

Source: Cell Reports

DOI: 10.1016/j.celrep.2014.08.055

Authors: Raffaella Di Micco, Barbara Fontanals-Cirera, Vivien Low, Panagiotis Ntziachristos, Stephanie K. Yuen, Claudia D. Lovell, Igor Dolgalev, Yoshiya Yonekubo, Guangtao Zhang, Elena Rusinova, Guillermo Gerona-Navarro, Marta Cañamero, Michael Ohlmeyer, Iannis Aifantis, Ming-Ming Zhou, Aristotelis Tsirigos, Eva Hernando

Institutions: NYU Langone Health, NYU Langone’s Laura and Isaac Perlmutter Cancer Center, New York University, Howard Hughes Medical Institute, Icahn School of Medicine at Mount Sinai, Spanish National Cancer Research Centre

Language: English

Topic: Pluripotent Stem Cells Research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $5,620

Funders: Howard Hughes Medical Institute, New York Stem Cell Foundation, National Institutes of Health, National Human Genome Research Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases

OpenAlex ID: W2027773301