Epigenetic resetting in the human germline entails histone modification remodelling [ChIP-Seq]

Epigenetic resetting in the mammalian germ line entailsacute DNA demethylation, which lays the foundation for gametogenesis, totipotency,and embryonic development. We characterize the epigenome of hypomethylated human primordial germ cells (hPGCs) to reveal mechanisms preventing the widespread derepression of genesand transposable elements (TEs). Along with the loss of DNA methylation, we show that hPGCsexhibit a profound reduction of repressive histone modifications resulting in diminished heterochromatic signaturesat most genesand TEsand the acquisition of a neutral or paused epigenetic state without transcriptional activation.Efficient maintenance of a heterochromatic state is limited to a subset of genomic loci, such asevolutionarily young TEsand some developmental genes, which require H3K9me3 and H3K27me3, respectively, forefficient transcriptional repression. Accordingly, transcriptional repression in hPGCs presentsan exemplary balanced system relying on local maintenance of heterochromatic featuresand a lack of inductive cues. Histone modifications ULI-NChIP-seq of human primordial germ cells gonadal somatic cells (two biological replicates for each cell type and sex)