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Human Sperm Epigenomes and Transcriptomes Reveal Novel Features of Enhancers, Sex Chromosomes, piRNAs, Gametogenesis, and Inherited Small RNAs

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE40196 | GEO | 2018/12/03

REPOSITORIES: GEO

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Human Sperm Epigenomes and Transcriptomes Reveal Novel Features of Enhancers, Sex Chromosomes, piRNAs, Gametogenesis, and Inherited Small RNAs (RNA-Seq)

Project description:To better understand the paternally inherited epigenome and transcriptome, we profiled multiple histone modifications, histone H3.3 variant, cytosine DNA methylation at base-pair resolution, and small RNA transcriptomes. We report new and surprising features of enhancers, pluripotency factor targets, spermiogenesis genes, piRNA clusters, CpG islands, partially methylated domains, imprinted loci, repetitive elements and sex chromosomes. First, we find that enhancers for embryonic transcription factors bear H3K27me3, but low H3K14ac and DNA methylation -- consistent with poising for future activation -- whereas enhancers near genes active in gametogenesis have high H3K27ac/H3K14ac, consistent with past activation. Second, binding site regions (in ES cells) for the pluripotency factors SOX2 and NANOG are DNA methylated in sperm, suggesting a need for zygotic demethylation/reprogramming. Unexpectedly, genes for spermiogenesis (but not spermatogenesis), and almost half of piRNA cluster promoters, bear both H3K4me3 and DNA methylation, a co-incidence not previously observed in mammals. Furthermore, we find major assymetries in H3.3 and H3K9me3 density between the X and Y chromosomes after MSCI. Lastly, deep sequencing reveals >10-fold increase in the known repertoire of retained/inherited miRNAs and piRNAs than previous estimates. Thus, the paternal epigenome contributes a mosaic of epigenetic regions that reflect past gametogenesis or poising for subsequent embryonic developmental regulation -- and a complex repertoire of small RNAs.

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