title: Peptidylarginine deiminase 1-catalyzed histone citrullination is essential for early embryo development.
abstract: Peptidylarginine deiminase (PADI) enzymes are increasingly being associated with the regulation of chromatin structure and gene activity via histone citrullination. As one of the PADI family members, PADI1 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 PADI1 in preimplantation development have not been addressed. Using a PADI1-specific 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 PADI1 or inhibition of PADI1 enzyme activity. Additionally, by employing 5-ethynyl uridine (EU) incorporation analysis, ablation of PADI1 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 PADI1. Thus, our data reveal a novel function of PADI1 during early embryo development transitions by catalyzing histone tail citrullination, which facilitates early embryo genome transactivation.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, Nanjing, China.|Department of Microbiology, Nanjing Medical University, Nanjing, China.
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Muth
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Thompson
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Coonrod
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Xuesen
authors.initials: X
authors.lastname: Zhang
mesh_terms: D002384:Catalysis; D000076302:Citrullination; D047108:Embryonic Development; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D006867:Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D000080062:Protein-Arginine Deiminase Type 1
chemical_list: D006657:Histones; D006867:Hydrolases; D000080062:Protein-Arginine Deiminase Type 1