Chromatin-to-nucleoprotamine transition is controlled by the histone H2B variant TH2B

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Montellier, Emilie | Boussouar, Fayçal | Rousseaux, Sophie | Zhang, Kai | Buchou, Thierry | Fenaille, François | Shiota, Hitoshi | Debernardi, Alexandra | Héry, Patrick | Curtet, Sandrine | Jamshidikia, Mahya | Barral, Sophie | Holota, Hélène | Bergon, Aurélie | Lopez, Fabrice | Guardiola, Philippe | Pernet, Karin | Imbert, Jean | Petosa, Carlo | Tan, Minjia | Zhao, Yingming | Gérard, Matthieu | Khochbin, Saadi

Edité par CCSD ; Cold Spring Harbor Laboratory Press -

International audience. 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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