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

Abstract

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.

How mammals pack their sperm: a variant matter

“…In their present study, Montellier et al (2013) report that in the absence of TH2B, core histones exhibit differential PTMs. Namely, histone H3K122 and H4K77 crotonylation were more abundant, and the position of these residues relative to the DNA backbone suggests a potential disruptive effect on nucleosomal structure.…”

“…The work of Montellier et al (2013) shows that TH2B is depleted in the two nucleosomes that surround TSSs and are known to be enriched in another testis-specific variant, H2A.Lap1 (Soboleva et al 2012). Similarly, the sex chromosome-specific replacement of H3 for H3.3 provides another example of regulated chromatin structure in spermatogenesis (van der Heijden et al 2007).…”

“…Indeed, most of the histones that assemble into the paternal pronucleus are of maternal origin. Here, the Kochbin team (Montellier et al 2013). demonstrates that TH2B, previously thought to be testis-specific, is also present in the maternal chromatin prior to fertilization and that it is incorporated into the male pronucleus of the zygote rapidly thereafter.…”

“…Now, in this issue of Genes & Development, Montellier et al (2013) document that TH2B is expressed in spermatocytes and spermatids, and its presence inversely correlates with the presence of canonical H2B, suggesting that TH2B gradually replaces H2B on chromatin, making it the first histone variant to be deposited on a genome-wide scale during spermiogenesis.…”

DOHaD et programmation pré- et péri-conceptionnelle

“…Ainsi, lors du remplacement des protamines du génome spermatique par les histones, certains variants d'histones, d'origine maternelle, présentent une asymétrie d'allocation. C'est le cas chez la souris, pour le variant H3.3 qui présente un biais en faveur du génome paternel [7], alors que TH2B (testis specific H2B), préalable-ment présent sur le génome maternel, est rapidement incorporé dans le pronoyau paternel [8,9]. Toujours chez la souris, les études montrent par ailleurs que, dès le remplacement des protamines, les histones associées au génome paternel sont hyperacétylées, alors que la méthylation persiste sur les histones associées au génome maternel [6].…”