Trrap-dependent histone acetylation specifically regulates cell-cycle gene transcription to control neural progenitor fate decisions

Academic Article

Abstract

  • Fate decisions in neural progenitor cells are orchestrated via multiple pathways, and the role of histone acetylation in these decisions has been ascribed to a general function promoting gene activation. Here, we show that the histone acetyltransferase (HAT) cofactor transformation/transcription domain-associated protein (Trrap) specifically regulates activation of cell-cycle genes, thereby integrating discrete cell-intrinsic programs of cell-cycle progression and epigenetic regulation of gene transcription in order to control neurogenesis. Deletion of Trrap impairs recruitment of HATs and transcriptional machinery specifically to E2F cell-cycle target genes, disrupting their transcription with consequent cell-cycle lengthening specifically within cortical apical neural progenitors (APs). Consistently, Trrap conditional mutants exhibit microcephaly because of premature differentiation of APs into intermediate basal progenitors and neurons, and overexpressing cell-cycle regulators in vivo can rescue these premature differentiation defects. These results demonstrate an essential and highly specific role for Trrap-mediated histone regulation in controlling cell-cycle progression and neurogenesis. © 2014 Elsevier Inc.
  • Authors

    Published In

  • Cell Stem Cell  Journal
  • Digital Object Identifier (doi)

    Author List

  • Tapias A; Zhou ZW; Shi Y; Chong Z; Wang P; Groth M; Platzer M; Huttner W; Herceg Z; Yang YG
  • Start Page

  • 632
  • End Page

  • 643
  • Volume

  • 14
  • Issue

  • 5