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Mol Cell. 2017 Apr 6;66(1):89-101.e8. doi: 10.1016/j.molcel.2017.02.025. Epub 2017 Mar 30.

Histone Variant H2A.L.2 Guides Transition Protein-Dependent Protamine Assembly in Male Germ Cells.

Author information

1
CNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, France.
2
CNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, France; Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Research Institute for Science and Engineering, Institute for Medical-oriented Structural Biology, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
3
Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Research Institute for Science and Engineering, Institute for Medical-oriented Structural Biology, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
4
Université Grenoble Alpes, Inserm U1038, CEA, BIG-BGE, Grenoble 38000, France.
5
Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette 91198, France.
6
TGML, platform IbiSA, Aix Marseille Univ, Inserm U1090, TAGC, Marseille 13288, France.
7
Laboratoire d'Etude du Métabolisme des Médicaments, DSV/iBiTec-S/SPI, CEA Saclay, Gif-sur-Yvette 91191 Cedex, France.
8
CNRS UMR 5309, Inserm U1209, Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38700, France. Electronic address: saadi.khochbin@univ-grenoble-alpes.fr.

Abstract

Histone replacement by transition proteins (TPs) and protamines (Prms) constitutes an essential step for the successful production of functional male gametes, yet nothing is known on the underlying functional interplay between histones, TPs, and Prms. Here, by studying spermatogenesis in the absence of a spermatid-specific histone variant, H2A.L.2, we discover a fundamental mechanism involved in the transformation of nucleosomes into nucleoprotamines. H2A.L.2 is synthesized at the same time as TPs and enables their loading onto the nucleosomes. TPs do not displace histones but rather drive the recruitment and processing of Prms, which are themselves responsible for histone eviction. Altogether, the incorporation of H2A.L.2 initiates and orchestrates a series of successive transitional states that ultimately shift to the fully compacted genome of the mature spermatozoa. Hence, the current view of histone-to-nucleoprotamine transition should be revisited and include an additional step with H2A.L.2 assembly prior to the action of TPs and Prms.

KEYWORDS:

Brdt; H2A.Z; MCM; Nap1L4; Npm3; SRCAP; TH2B; Tip60; spermiogenesis; subnucleosome

PMID:
28366643
DOI:
10.1016/j.molcel.2017.02.025
[Indexed for MEDLINE]
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