Dynamics of histone acetylation during human early embryogenesis

Abstract

AbstractIt remains poorly understood about the regulation of gene and transposon transcription during human early embryogenesis. Here, we report that broad H3K27ac domains are genome-widely distributed in human 2-cell and 4-cell embryos and transit into typical peaks in the 8-cell embryos. The broad H3K27ac domains in early embryos before zygotic genome activation (ZGA) are also observed in mouse. It suggests that broad H3K27ac domains play conserved functions before ZGA in mammals. Intriguingly, a large portion of broad H3K27ac domains overlap with broad H3K4me3 domains. Further investigation reveals that histone deacetylases are required for the removal or transition of broad H3K27ac domains and ZGA. After ZGA, the number of typical H3K27ac peaks is dynamic, which is associated with the stage-specific gene expression. Furthermore, P300 is important for the establishment of H3K27ac peaks and the expression of associated genes in early embryos after ZGA. Our data also indicate that H3K27ac marks active transposons in early embryos. Interestingly, H3K27ac and H3K18ac signals rather than H3K9ac signals are enriched at ERVK elements in mouse embryos after ZGA. It suggests that different types of histone acetylations exert distinct roles in the activation of transposons. In summary, H3K27ac modification undergoes extensive reprogramming during early embryo development in mammals, which is associated with the expression of genes and transposons.