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Nut directs p300-dependant genome-wide H4 hyperacetylation in male germ cells: transcriptomic data

ABSTRACT: NUT, nuclear protein in testis, is a universal oncogenic driver in the highly aggressive NUT Midline Carcinoma whose physiological function in male germ cells had so far remained unknown. Here we show that Nut’s expression is normally restricted to post-meiotic spermatogenic cells, where its presence triggers the p300-dependant 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. Molecular investigations show that Nut uses CBP/p300 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 has long been known to occur prior to the final compaction of the male genome.

ORGANISM(S): Mus musculus

PROVIDER: GSE118969 | GEO | 2018/10/15

REPOSITORIES: GEO

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Nut is a cell type-specific stimulator of p300 enhancing H4 hyperacetylation during haploid male genome programming

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