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Cited by 51Pluripotent Stem Cells ResearchEpigenetics and DNA MethylationGenomics and Chromatin Dynamics

TAF5L and TAF6L Maintain Self-Renewal of Embryonic Stem Cells via the MYC Regulatory Network

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Seruggia, Davide, Oti, Martin, Tripathi, Pratibha, Canver, Matthew C., LeBlanc, Lucy, Di Giammartino, Dafne C., Bullen, Michael J., Nefzger, Christian M. +8 more·2019·Molecular Cell
DOI 10.1016/j.molcel.2019.03.025PMC PMC6671628
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Abstract

Self-renewal and pluripotency of the embryonic stem cell (ESC) state are established and maintained by multiple regulatory networks that comprise transcription factors and epigenetic regulators. While much has been learned regarding transcription factors, the function of epigenetic regulators in these networks is less well defined. We conducted a CRISPR-Cas9-mediated loss-of-function genetic screen that identified two epigenetic regulators, TAF5L and TAF6L, components or co-activators of the GNAT-HAT complexes for the mouse ESC (mESC) state. Detailed molecular studies demonstrate that TAF5L/TAF6L transcriptionally activate c-Myc and Oct4 and their corresponding MYC and CORE regulatory networks. Besides, TAF5L/TAF6L predominantly regulate their target genes through H3K9ac deposition and c-MYC recruitment that eventually activate the MYC regulatory network for self-renewal of mESCs. Thus, our findings uncover a role of TAF5L/TAF6L in directing the MYC regulatory network that orchestrates gene expression programs to control self-renewal for the maintenance of mESC state.

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Authors
Seruggia, D., Oti, M., Tripathi, P., Canver, M. C., LeBlanc, L., Di Giammartino, D. C., Bullen, M. J., Nefzger, C. M., Sun, Y. B. Y., Farouni, R., Polo, J. M., Pinello, L., Apostolou, E., Kim, J., Orkin, S. H., & Das, P. P.
Affiliations
  • Boston Children's Hospital (US)
  • Monash University (AU)
  • The University of Texas at Austin (US)
  • Australian Regenerative Medicine Institute (AU)
  • Harvard University (US)
  • Weill Cornell Medicine (US)
Corresponding author
  • Orkin, Stuart H.
  • Das, Partha Pratim
ORCID
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2019-06
Volume
74
Issue
6
Pages
1148-1163.e7
ISSN
1097-2765 (ISSN-L)
DOI
10.1016/j.molcel.2019.03.025
PMC
PMC6671628
OpenAlex
W2936193003
Cited by
51
References
4
Citations by year
2026: 6 · 2025: 5 · 2024: 9 · 2023: 4 · 2022: 4 · 2021: 10 · 2020: 11 · 2019: 2
FWCI
2.23
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
Funders
  • NIH (HLBI U01HL100001, R01GM112722, DP2DA043813)
  • National Health and Medical Research Council (GNT1159461)
  • National Institute of Diabetes and Digestive and Kidney Diseases (F30-DK103359)
  • National Human Genome Research Institute (R00HG008399)
  • Sylvia and Charles Viertel
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
embryonic stem cell self-renewal, epigenetic regulators, c-Myc, Oct4, H3K9 acetylation, transcriptional activation, pluripotency, mouse embryonic stem cells, CRISPR-Cas9 loss-of-function screen
MeSH terms
Gene Editing, Animals, Cell Cycle, Embryo, Mammalian, Fibroblasts, Gene Expression Regulation, Histones, Humans, Signal Transduction, Proto-Oncogene Proteins c-myc, Protein Isoforms, TATA-Binding Protein Associated Factors, Epigenesis, Genetic, Cell Proliferation, Mice, Gene Regulatory Networks, Embryonic Stem Cells, Induced Pluripotent Stem Cells, HEK293 Cells, Primary Cell Culture, CRISPR-Cas Systems, Cellular Reprogramming

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