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Cell Stem Cell. 2014 May 1;14(5):632-43. doi: 10.1016/j.stem.2014.04.001.

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

Author information

1
Leibniz Institute for Age Research, Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, 07745 Jena, Germany.
2
Disease Genomics and Individualized Medicine Laboratory, Beijing Institute of Genomics, Chinese Academy of Sciences, 1-7 Beichen West Road, Chaoyang District, Beijing 100101, P.R. China; University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, P.R. China.
3
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
4
International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, 69008 Lyon, France.
5
Leibniz Institute for Age Research, Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, 07745 Jena, Germany; Faculty of Biology and Pharmacy, Friedrich Schiller University of Jena, Fuerstengraben 26, 07743 Jena, Germany. Electronic address: zqwang@fli-leibniz.de.

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.

PMID:
24792116
DOI:
10.1016/j.stem.2014.04.001
[Indexed for MEDLINE]
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