Fam60a defines a variant Sin3a-Hdac complex in embryonic stem cells required for self-renewal

Gundula Streubel, Darren J. Fitzpatrick, Giorgio Oliviero, Andrea Scelfo, Bruce Moran, Sudipto Das, Nayla Munawar, Ariane Watson, Kieran Wynne, Gian Luca Negri, Eugene T. Dillon, Sri Ganesh Jammula, Karsten Hokamp, Darran P. O'Connor, Diego Pasini, Gerard Cagney, Adrian P. Bracken

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Sin3a is the central scaffold protein of the prototypical Hdac1/2 chromatin repressor complex, crucially required during early embryonic development for the growth of pluripotent cells of the inner cell mass. Here, we compare the composition of the Sin3a-Hdac complex between pluripotent embryonic stem (ES) and differentiated cells by establishing a method that couples two independent endogenous immunoprecipitations with quantitative mass spectrometry. We define the precise composition of the Sin3a complex in multiple cell types and identify the Fam60a subunit as a key defining feature of a variant Sin3a complex present in ES cells, which also contains Ogt and Tet1. Fam60a binds on H3K4me3-positive promoters in ES cells, together with Ogt, Tet1 and Sin3a, and is essential to maintain the complex on chromatin. Finally, we show that depletion of Fam60a phenocopies the loss of Sin3a, leading to reduced proliferation, an extended G1-phase and the deregulation of lineage genes. Taken together, Fam60a is an essential core subunit of a variant Sin3a complex in ES cells that is required to promote rapid proliferation and prevent unscheduled differentiation.

Original languageEnglish
Pages (from-to)2216-2232
Number of pages17
JournalEMBO Journal
Volume36
Issue number15
DOIs
Publication statusPublished - Aug 1 2017
Externally publishedYes

Keywords

  • Fam60a
  • Sin3a-Hdac complex
  • embryonic stem cell
  • self-renewal

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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