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

Mol Cell. 2019 Jun 20;74(6):1148-1163.e7. doi: 10.1016/j.molcel.2019.03.025. Epub 2019 Apr 17.


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.


Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CRISPR-Cas Systems
  • Cell Cycle / genetics
  • Cell Proliferation
  • Cellular Reprogramming
  • Embryo, Mammalian
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Epigenesis, Genetic
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Editing
  • Gene Expression Regulation
  • Gene Regulatory Networks*
  • HEK293 Cells
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism*
  • Mice
  • Primary Cell Culture
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism
  • Signal Transduction
  • TATA-Binding Protein Associated Factors / genetics*
  • TATA-Binding Protein Associated Factors / metabolism


  • Histones
  • Myc protein, mouse
  • Protein Isoforms
  • Proto-Oncogene Proteins c-myc
  • TATA-Binding Protein Associated Factors
  • Taf5l protein, mouse
  • Taf6l protein, mouse