Journal
GENES & DEVELOPMENT
Volume 27, Issue 15, Pages 1680-1692Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.220095.113
Keywords
H2AZ; BRDT; male contraception; reprogramming; male infertility; sex chromosome inactivation; histone eviction
Categories
Funding
- ANR EpiSperm2 grant
- INCa
- ARC libre'' funds
- MTR bourse flechee
- ARC fellowship
- European Commission
- contrat jeune chercheur'' INSERM
- IBiSA, Aix-Marseille Universite
- [ANR-10-INBS-0009-10]
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The conversion of male germ cell chromatin to a nucleoprotamine structure is fundamental to the life cycle, yet the underlying molecular details remain obscure. Here we show that an essential step is the genome-wide incorporation of TH2B, a histone H2B variant of hitherto unknown function. Using mouse models in which TH2B is depleted or C-terminally modified, we show that TH2B directs the final transformation of dissociating nucleosomes into protamine-packed structures. Depletion of TH2B induces compensatory mechanisms that permit histone removal by up-regulating H2B and programming nucleosome instability through targeted histone modifications, including lysine crotonylation and arginine methylation. Furthermore, after fertilization, TH2B reassembles onto the male genome during protamine-to-histone exchange. Thus, TH2B is a unique histone variant that plays a key role in the histone-to-protamine packing of the male genome and guides genome-wide chromatin transitions that both precede and follow transmission of the male genome to the egg.
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