Biparental contributions of the < i > H2A < /i > . < i > B < /i > histone variant control embryonic development in mice

by Antoine Molaro, Anna J. Wood, Derek Janssens, Selina M. Kindelay, Michael T. Eickbush, Steven Wu, Priti Singh, Charles H. Muller, Steven Henikoff, Harmit S. Malik

Histone variants expand chromatin functions in eukaryote genomes.H2A.B genes are testis-expressed short histone H2A variants that arose in placental mammals. Their biological functions remain largely unknown. To investigate their function, we generated a knockout (KO) model that disrupts all 3H2A.B genes in mice. We show thatH2A.B KO males have globally altered chromatin structure in postmeiotic germ cells. Yet, they do not show impaired spermatogenesis or testis function. Instead, we find thatH2A.B plays a crucial role postfertilization. Crosses betweenH2A.B KO males and females yield embryos with lower viability and reduced size. Using a series of genetic crosses that separate parental and zygotic contributions, we show that theH2A.B status of both the father and mother, but not of the zygote, affects embryonic viability and growth during gestation. We conclude thatH2A.B is a novel parental-effect gene, establishing a role for short H2A histone variants in mammalian development. We posit that parental antagonism over embryonic growth drove the origin and ongoing diversification of short histone H2A variants in placental mammals.

Source: PLoS Biology: Archived Table of Contents - December 23, 2020 Category: Biology Authors: Antoine Molaro Source Type: research