Dynamic nucleosome remodeling mediated by YY1 underlies early mouse development

Nucleosome positioning can alter the accessibility of DNA-binding proteins to their cognate DNA elements, and thus its precise control is essential for cell identity and function. Mammalian preimplantation embryos undergo temporal changes in gene expression and cell potency, suggesting the involvement of dynamic epigenetic control during this developmental phase. However, the dynamics of nucleosome organization during early development are poorly understood. In this study, using a low-input MNase-seq method, we show that nucleosome positioning is globally obscure in zygotes but becomes well defined during subsequent development. Downregulation of the chromatin assembly in embryonic stem cells can partially reverse nucleosome organization into a zygote-like pattern, suggesting that the chromatin assembly pathway might be linked to fuzzy nucleosomes in zygotes. We also reveal that YY1, a zinc finger containing transcription factor expressed upon zygotic genome activation, regulates the de novo formation of well-positioned nucleosome arrays at the regulatory elements, through identifying YY1-binding sites in 8-cell embryos. The YY1-binding regions acquire H3K27ac enrichment around the 8-cell and morula stages and YY1 depletion impairs the morula-to-blastocyst transition. Thus, our study delineates the remodeling of nucleosome organization and its underlying mechanism during early mouse development. Low-input MNase-seq, RNA-seq, and CUT&RUN have been performed for mouse early embryos and ESCs.