Peptidylarginine deiminase 1-catalyzed histone citrullination is essential for early embryo development.

Peptidylarginine deiminase enzymes are increasingly being associated with the regulation of chromatin structure and gene activity via histone citrullination. As one of the family members, has been mainly reported to be expressed in the epidermis and uterus, where the protein in keratinocytes is thought to promote differentiation by citrullinating filament proteins. However, the roles of duanyu1563I1 in preimplantation development have not been addressed. Using a inhibitor and Padi1-morpholino knockdown, we found that citrullination of histone tails at H4R3 and H3R2/8/17 were markedly reduced in the 2- and 4-cell embryos. Consistent with this observation, early embryo development was also arrested at the 4-cell stage upon depletion of duanyu1563I1 or inhibition of duanyu1563I1 enzyme activity. Additionally, by employing 5-ethynyl uridine (EU) incorporation analysis, ablation of duanyu1563I1 function led to a dramatic decrease in overall transcriptional activity, correlating well with the reduced levels of phosphorylation of RNA Pol II at Ser2 observed at 2- or 4-cell stage of embryos under Padi1 knockdown or inhibiting Thus, our data reveal a novel function of duanyu1563I1 during early embryo development transitions by catalyzing histone tail citrullination, which facilitates early embryo genome transactivation.

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