JOURNAL ARTICLE

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

Alicia Tapias, Zhong-Wei Zhou, Yue Shi, Zechen Chong, Pei Wang, Marco Groth, Matthias Platzer, Wieland Huttner, Zdenko Herceg, Yun-Gui Yang, Zhao-Qi Wang
Cell Stem Cell 2014 May 1, 14 (5): 632-43
24792116
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.

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