Chromatin analysis in human early development reveals epigenetic transition during ZGA

Abstract

Upon fertilization, drastic chromatin reorganization occurs during preimplantation development . However, the global chromatin landscape and its molecular dynamics in this period remain largely unexplored in humans. Here we investigate chromatin states in human preimplantation development using an improved assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) . We find widespread accessible chromatin regions in early human embryos that overlap extensively with putative cis-regulatory sequences and transposable elements. Integrative analyses show both conservation and divergence in regulatory circuitry between human and mouse early development, and between human pluripotency in vivo and human embryonic stem cells. In addition, we find widespread open chromatin regions before zygotic genome activation (ZGA). The accessible chromatin loci are readily found at CpG-rich promoters. Unexpectedly, many others reside in distal regions that overlap with DNA hypomethylated domains in human oocytes and are enriched for transcription factor-binding sites. A large portion of these regions then become inaccessible after ZGA in a transcription-dependent manner. Notably, such extensive chromatin reorganization during ZGA is conserved in mice and correlates with the reprogramming of the non-canonical histone mark H3K4me3, which is uniquely linked to genome silencing. Taken together, these data not only reveal a conserved principle that underlies the chromatin transition during mammalian ZGA, but also help to advance our understanding of epigenetic reprogramming during human early development and in vitro fertilization.

Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation

“…Our finding that chromatin accessibility increases during genome activation, especially at promoter and enhancer elements, is consistent with recent studies in Drosophila, zebrafish, Xenopus, mouse and human embryos [4,[10][11][12][13]25,49]. An increase in the number and strength of ATAC-seq peaks over time may either be due to an increase in the number of cells in which specific regions are accessible, or an actual increase in the accessibility of specific regions in all cells of the embryo.…”

“…Similarly, a subset of promoters in human and mouse embryos exhibit open chromatin prior to activation of the genome [4,11,12]. We conclude that the establishment of accessible chromatin prior to gene activity is a common theme during early development.…”

Persistent chromatin states, pervasive transcription, and sharedcis-regulatory sequences have shaped theC. elegansgenome

“…We had anticipated that histone modifications of Pol II transcription would appear progressively during embryogenesis, in a manner similar to the activation of cis-regulatory regions mapped in Drosophila and mammalian embryos (Blythe and Wieschaus 2016;Hug et al 2017;Wu et al 2018). However, we find evidence that H3K27ac and H3K4me2 are present in the earliest stages of embryogenesis (60 minutes PF) prior to the broad phase of transcriptional upregulation at gastrulation.…”

Single‐cell RNA‐seq reveals distinct dynamic behavior of sex chromosomes during early human embryogenesis

“…Guo et al, 2015; Y. Hou et al, 2013;Wu et al, 2018), including the generation of comprehensive transcriptional atlases (Deng et al, 2014;Petropoulos et al, 2016;Xue et al, 2013;Yan et al, 2013). Here we aimed to determine to what extent male and female embryos differ in relation to gene expression levels during early development.…”