Molecular Cell
Volume 66, Issue 1, 6 April 2017, Pages 89-101.e8
Journal home page for Molecular Cell

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

https://doi.org/10.1016/j.molcel.2017.02.025Get rights and content
Under an Elsevier user license
open archive

Highlights

  • H2A.L.2 and transition proteins (TPs) are co-expressed in post-meiotic germ cells

  • Lack of H2A.L.2 leads to defective spermatozoa genome compaction and male infertility

  • H2A.L.2 assembly opens nucleosomes, releases flexible DNA ends, and allows TP loading

  • TP loading drives protamine processing and organized compaction of the sperm genome

Summary

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

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

Cited by (0)

7

Co-first author

8

Lead Contact