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Title: Nut Directs p300-Dependent, Genome-Wide H4 Hyperacetylation in Male Germ Cells.
Authors: Shiota, H
Barral, S
Buchou, T
Tan, M
Couté, Y
Charbonnier, G
Reynoird, N
Boussouar, F
Gérard, M
Zhu, M
Bargier, L
Puthier, D
Chuffart, F
Bourova-Flin, E
Picaud, S
Filippakopoulos, P
Goudarzi, A
Ibrahim, Z
Panne, D
Rousseaux, S
Zhao, Y
Khochbin, S
First Published: 25-Sep-2018
Publisher: Elsevier (Cell Press)
Citation: Cell Reports, 2018, 24 (13), pp. 3477-3487.e6
Abstract: Nuclear protein in testis (Nut) is a universal oncogenic driver in the highly aggressive NUT midline carcinoma, whose physiological function in male germ cells has been unclear. Here we show that expression of Nut is normally restricted to post-meiotic spermatogenic cells, where its presence triggers p300-dependent genome-wide histone H4 hyperacetylation, which is essential for the completion of histone-to-protamine exchange. Accordingly, the inactivation of Nut induces male sterility with spermatogenesis arrest at the histone-removal stage. Nut uses p300 and/or CBP to enhance acetylation of H4 at both K5 and K8, providing binding sites for the first bromodomain of Brdt, the testis-specific member of the BET family, which subsequently mediates genome-wide histone removal. Altogether, our data reveal the detailed molecular basis of the global histone hyperacetylation wave, which occurs before the final compaction of the male genome.
DOI Link: 10.1016/j.celrep.2018.08.069
eISSN: 2211-1247
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2018. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: The accession number for the raw and processed MNase sequencing data reported in this paper is GEO: GSE111931. The accession number for the raw and processed transcriptomic Illumina data reported in this paper is GEO: GSE118969. Proteomic data: the list of all identified proteins immunoprecipitated by the anti-Nut antibody has been deposited with ProteomeXchange consortium via the PRIDE database with the accession number: PXD008727.
Appears in Collections:Published Articles, Dept. of Molecular and Cell Biology

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