Chromatin-to-nucleoprotamine transition is controlled by the histone H2B variant TH2B
- Emilie Montellier1,
- Fayçal Boussouar1,
- Sophie Rousseaux1,
- Kai Zhang2,
- Thierry Buchou1,
- François Fenaille3,
- Hitoshi Shiota1,
- Alexandra Debernardi1,
- Patrick Héry4,
- Sandrine Curtet1,
- Mahya Jamshidikia1,
- Sophie Barral1,
- Hélène Holota5,
- Aurélie Bergon5,
- Fabrice Lopez5,
- Philippe Guardiola6,
- Karin Pernet7,
- Jean Imbert5,
- Carlo Petosa8,
- Minjia Tan9,10,
- Yingming Zhao9,10,
- Matthieu Gérard4 and
- Saadi Khochbin1,11
- 1U823, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Albert Bonniot, Université Joseph Fourier, Grenoble F-38700 France;
- 2State Key Laboratory of Medicinal Chemical Biology, Department of Chemistry, Nankai University, Tianjin 300071, China;
- 3Laboratoire d'Etude du Métabolisme des Médicaments, Direction des sciences du vivant (DSV), Institut de Biologie et de Technologies de Saclay (iBiTec-S), Institut de Biologie et de Technologies de Saclay (SPI), Commissariat à l'Energie Atomique et aux Énergies Alternatives (CEA) Saclay, Gif sur Yvette 91191, Cedex, France;
- 4iBiTec-S, CEA, Gif-sur-Yvette F-91191 France;
- 5UMR_S 1090, INSERM, France; TGML/TAGC, Aix-Marseille Université, Marseille, France;
- 6U892, INSERM, Centre de Recherche sur le Cancer Nantes Angers, UMR_S 892, Université d'Angers, Plateforme SNP, Transcriptome and Epigénomique; Centre Hospitalier Universitaire d'Angers, Angers F-49000, France;
- 7U836 INSERM, Grenoble Institute of Neuroscience, Université Joseph Fourier, Grenoble F-38700, France;
- 8University Grenoble Alpes, Centre National de la Recherche Scientifique (CNRS), CEA, Institut de Biologie Structurale, Grenoble 38027, France;
- 9Ben May Department of Cancer Research, University of Chicago, Chicago, Illinois 60637, USA;
- 10Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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.
Keywords
- H2AZ
- BRDT
- male contraception
- reprogramming
- male infertility
- sex chromosome inactivation
- histone eviction
Footnotes
-
↵11 Corresponding author
E-mail khochbin{at}ujf-grenoble.fr
-
Supplemental material is available for this article.
-
Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.220095.113.
- Received April 16, 2013.
- Accepted June 26, 2013.
- Copyright © 2013 by Cold Spring Harbor Laboratory Press