Project description:The R-loop is a common chromatin feature presented from prokaryotic to eukaryotic genomes and has been revealed to be involved in multiple cellular processes. Here, we developed a novel R-loop profiling technique, ULI-ssDRIP-seq, to decte global R-loops from a limited number of cells. Based on this method, we profiled the R-loop landscapes during parental-to-zygotic transition and early development regulatory in zebrafish, and revealed a series of important characters of R-loops.
Project description:The epigenome plays critical roles in controlling gene expression and development. However, how the parental epigenomes transit to the zygotic epigenome in early development remains elusive. Here, we show parental-to-zygotic transition in zebrafish involves extensive erasure of parental epigenetic memory starting by methylating gametic enhancers. Surprisingly, this occurs even prior to fertilization for sperm. Both parental enhancers lose histone marks by the 4-cell stage, and zygotic enhancers are not activated until around zygotic genome activation (ZGA). By contrast, many promoters remain hypomethylated and, unexpectedly, acquire de novo histone acetylation as early as at the 4-cell stage. They then resolve into either activated or repressed promoters upon ZGA. Maternal depletion of histone acetyltransferases results in aberrant ZGA and early embryonic lethality. Finally, such reprogramming is largely driven by maternal factors with zygotic products contributing to embryonic enhancer activation. Thus, these data revealed widespread enhancer dememorization and promoter priming during parental-to-zygotic transition.
Project description:Histone modifications regulate gene expression and development. To address how they are reprogrammed in human early development, we investigated key histone marks in human oocytes and early embryos. Unlike that in mouse, the permissive mark H3K4me3 largely exhibits canonical patterns at promoters in human oocytes. After fertilization, pre-zygotic genome activation (ZGA) embryos acquire permissive chromatin and widespread H3K4me3 in CpG-rich regulatory regions. By contrast, the repressive mark H3K27me3 undergoes global depletion. CpG-rich regulatory regions then resolve to either active or repressed states upon ZGA, followed by subsequent restoration of H3K27me3 at developmental genes. Finally, through combining chromatin and transcriptome maps, we revealed transcription circuitry and asymmetric H3K27me3 patterning during early lineage specification. Collectively, our data unveil a priming phase connecting human parental-to-zygotic epigenetic transition.
Project description:Maternal-to-zygotic transition (MZT) is a conserved and fundamental process during which the maternal environment of oocyte transits to the zygotic genome driven expression program, and terminally differentiated oocyte and sperm are reprogrammed to totipotency. Metaphase II (MII) oocytes and zygotes (one-cell embryo) serve as the mature oocyte and the initiation of pre-implantation embryo development respectively, and characterizing their molecular landscapes at protein levels plays an important role in uncovering MZT and zygotic genome activation (ZGA )in mammals. Here we used an ultrasensitive proteomic approach to depict an in-depth landscape for the very early stage of mouse MZT.
Project description:Maternal-to-zygotic transition (MZT) is a conserved and fundamental process during which the maternal environment of oocyte transits to the zygotic genome driven expression program, and terminally differentiated oocyte and sperm are reprogrammed to totipotency. It is initiated by maternal mRNAs and proteins during the period of zygotic genome quiescence after fertilization, followed by a gradual switch to zygotic genome activation and accompanied by clearance of maternal RNAs and proteins. A key question for embryonic development is how MZT process is regulated. Here we used a low-input proteomic analysis to measure the proteomic dynamics during early development of mouse maternal-to-zygotic transition.