Wei Xie’s group and Anming Meng’s group published research in Molecular Cell on epigenetic reprogramming during parental-to-zygotic transition in zebrafish
By investigating the reprogramming of histone modifications during parental-to-zygotic transition in vertebrates, a team led by two groups in the School of Life Sciences of Tsinghua University (Wei Xie’s group and Anming Meng’s group), has revealed the conserved “erase-and-rewrite” principle for epigenome transition through distinct paths during parental-to-zygotic transition in zebrafish. Their findings, published in Molecular Cell on Nov. 15, 2018, not only revealed a multi-step establishment of the zygotic epigenome in zebrafish but also shed light on the conservation and divergence of epigenetic reprogramming during early vertebrate development.
The epigenome plays a crucial role in gene regulation during animal development. Recent progress using highly sensitive technologies revealed the extensive erasure of parental epigenetic information after fertilization, with only some inherited to the progeny which plays a critical role in embryonic development. However, it remains elusive how the zygotic epigenome is established. In addition, as early development is highly divergent during evolution, it is unclear whether the epigenomic reprogramming modes are conserved among different species. Zebrafish, a non-mammalian vertebrate model, provides a chance to answer these questions due to its unique developmental features.
Firstly, there are about 10 cell cycles before zygotic genome activation (ZGA), endowing an extended time window to explore the epigenetic reprogramming during parental-to-zygotic transition. Secondly, unlike mammals, there are no protamine-histone exchanges or global DNA demethylation in zebrafish embryos. Using a combination of sensitive ChIP-seq methods developed from Wei Xie’s group (STAR ChIP-seq (Zhang et al., Nature, 2016)) and a novel genetic tool from Anming Meng’s group (Oocyte Microinjection in situ (Wu et al., JMCB, 2018)), they investigated the reprogramming and re-establishment of histone modifications from gametes to post-ZGA embryos.
Through the study of histone modifications in zebrafish gametes and early embryos, the researchers first systematically examined the genome-wide presence of H3K4me3, H3K27ac, H3K27me3 and H3K36me3 in sperm, oocyte, 4-cell, 256-cell and dome stage embryos. By comparing the epigenomes between gametes and early embryos, they found that parental epigenetic memory at enhancers is quickly erased after fertilization. Surprisingly, such “dememorization” of DNA methylation signatures starts even earlier prior to fertilization in the sperm. Histone marks at parental enhancers are already removed by the 4-cell stage, and the reactivation of zygotic enhancers does not occur until around ZGA. By contrast, the deposition of histone acetylation H3K27ac at hypomethylated regions occurs as early as the 4-cell stage, indicating an extensive priming event in promoters prior to ZGA. Upon ZGA, these promoters resolve themselves to become either repressed or activated promoters. Importantly, the maternal depletion of histone acetyltransferases results in aberrant ZGA and embryonic lethality. The resolution of primed promoters upon ZGA is largely driven by maternal factors while the re-activation of enhancers involves both maternal and zygotic regulators. Taken together, these data uncovered a theme of epigenetic reprogramming during parental-to-zygotic transition by “dememorizing” enhancers and priming promoters. Importantly, when compared to results in mouse embryos from earlier studies, they found similar “erase-and-rewrite” principles that are conserved between different species. Thus their work revealed divergent modes but conserved principles for epigenetic reprogramming during parental-to-zygotic transition in vertebrates.
A model shows the erasure of parental epigenomes and the "step-wise" establishment of zygotic epigenome at enhancers and promoters before and after ZGA in zebrafish
Prof. Wei Xie from the School of Life Sciences of Tsinghua University, and Prof. Anming Meng from the School of Life Sciences of Tsinghua University are the co-corresponding authors of this work. PhD students Bingjie Zhang and Xiaotong Wu, from the School of Life Sciences at Tsinghua University, and PhD student Wenhao Zhang, from the CLS-program of the School of Life Sciences at Tsinghua University, are the co-first authors of this work. The study was supported by funding from the National Key R&D Program of China, National Basic Research Program of China (973 program), the National Natural Science Foundation of China, funding from the THU-PKU Center for Life Sciences and the HHMI International Research Scholar Award, and also by the animal facility, the sequencing facility and the computation facility at Tsinghua University.
Paper link:
From School of Life Sciences
