Epigenetic homogeneity in histone methylation underlies sperm programming for embryonic transcription

Abstract

Sperm contributes genetic and epigenetic information to the embryo to efficiently support development. However, the mechanism underlying such developmental competence remains elusive. Here, we investigated whether all sperm cells have a common epigenetic configuration that primes transcriptional program for embryonic development. Using calibrated ChIP-seq, we show that remodelling of histones during spermiogenesis results in the retention of methylated histone H3 at the same genomic location in most sperm cell. This homogeneously methylated fraction of histone H3 in the sperm genome is maintained during early embryonic replication. Such methylated histone fraction resisting post-fertilisation reprogramming marks developmental genes whose expression is perturbed upon experimental reduction of histone methylation. A similar homogeneously methylated histone H3 fraction is detected in human sperm. Altogether, we uncover a conserved mechanism of paternal epigenetic information transmission to the embryo through the homogeneous retention of methylated histone in a sperm cells population.

Whole-genome sequencing of H3K4me3 and DNA methylation in human sperm reveals regions of overlap linked to fertility and development

“…These mouse models indicate that H3K4me3 is responsive to the environment and is linked to embryonic development and offspring health. Whether similar functions and H3K4me3 profiles are conserved in men is not known, and there are limitations in existing data on H3K4me3 because it is derived from only a few men (Hammoud et al, 2009(Hammoud et al, , 2011Oikawa et al, 2020).…”

Micrococcal nuclease sequencing of porcine sperm suggests a nucleosomal involvement on semen quality and early embryo development

“…A smaller SN band of ~ 100 bp was also identified. A SN band has been also detected in yeast [37], Xenopus laevis sperm [38] and human sperm [10] and may correspond to partially unwrapped nucleosomes that have lost one of the H2A and H2B dimers. Proteomic analysis of SN bands in Xenopus revealed association with chromatin regulatory proteins (H3, H4, H1FX, CBX3, WDR5) [38].…”

“…A SN band has been also detected in yeast [37], Xenopus laevis sperm [38] and human sperm [10] and may correspond to partially unwrapped nucleosomes that have lost one of the H2A and H2B dimers. Proteomic analysis of SN bands in Xenopus revealed association with chromatin regulatory proteins (H3, H4, H1FX, CBX3, WDR5) [38]. Other articles describe that these remodeling complexes can facilitate TF binding to SN when this includes their binding sequence.…”

Heterogeneity in the Epigenetic Landscape of Murine Testis-Specific Histone Variants TH2A and TH2B Sharing the Same Bi-Directional Promoter

“…The loci important for embryonic development and sperm function are marked by nucleosomes containing modified histones like H3K4me3 and H3K27me3. The chromatin states of these respective loci are correlative to their expression in early embryos ( Brykczynska et al, 2010 ; Jung et al, 2017 ; Oikawa et al, 2020 ).…”