Abstract：
:Zygotic genome activation (ZGA) is the first transcription event in life1. However, it is unclear how RNA polymerase is engaged in initiating ZGA in mammals. Here, by developing small-scale Tn5-assisted chromatin cleavage with sequencing (Stacc-seq), we investigated the landscapes of RNA polymerase II (Pol II) binding in mouse embryos. We found that Pol II undergoes 'loading', 'pre-configuration', and 'production' during the transition from minor ZGA to major ZGA. After fertilization, Pol II is preferentially loaded to CG-rich promoters and accessible distal regions in one-cell embryos (loading), in part shaped by the inherited parental epigenome. Pol II then initiates relocation to future gene targets before genome activation (pre-configuration), where it later engages in full transcription elongation upon major ZGA (production). Pol II also maintains low poising at inactive promoters after major ZGA until the blastocyst stage, coinciding with the loss of promoter epigenetic silencing factors. Notably, inhibition of minor ZGA impairs the Pol II pre-configuration and embryonic development, accompanied by aberrant retention of Pol II and ectopic expression of one-cell targets upon major ZGA. Hence, stepwise transition of Pol II occurs when mammalian life begins, and minor ZGA has a key role in the pre-configuration of transcription machinery and chromatin for genome activation.
journal_name
Naturejournal_title
Natureauthors
Liu B,Xu Q,Wang Q,Feng S,Lai F,Wang P,Zheng F,Xiang Y,Wu J,Nie J,Qiu C,Xia W,Li L,Yu G,Lin Z,Xu K,Xiong Z,Kong F,Liu L,Huang C,Yu Y,Na J,Xie Wdoi
10.1038/s41586-020-2847-ysubject
Has Abstractpub_date
2020-11-01 00:00:00pages
139-144issue
7832eissn
0028-0836issn
1476-4687pii
10.1038/s41586-020-2847-yjournal_volume
587pub_type
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