Trrap-dependent histone acetylation specifically regulates cell-cycle gene transcription to control neural progenitor fate decisions.
Cell Stem Cell, 2014/5/01;14(5):632-43.
Tapias A[1], Zhou ZW[1], Shi Y[2], Chong Z[2], Wang P[1], Groth M[1], Platzer M[1], Huttner W[3], Herceg Z[4], Yang YG[2], Wang ZQ[5]
Affiliations
PMID: 24792116
Impact factor: 25.269
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.
MeSH terms
Adaptor Proteins, Signal Transducing; Animals; Cell Cycle; Cell Cycle Proteins; Cell Differentiation; Cells, Cultured; Chromatin Immunoprecipitation; Female; Histone Acetyltransferases; Immunoblotting; In Situ Nick-End Labeling; Male; Mice; Mice, Transgenic; Models, Theoretical; Nuclear Proteins
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