title: WDR5 in porcine preimplantation embryos: expression, regulation of epigenetic modifications and requirement for early development†.
abstract: WD repeat-containing protein 5 (WDR5), a member of conserved WD40 protein family, is an essential component of the mixed lineage leukemia (MLL) complexes, which are crucial for numerous key biological processes including methylation of histone H3 lysine 4 (H3K4), self-renewal of embryonic stem cells, and formation of induced pluripotent stem cells. The expression pattern and functional role of WDR5 during porcine preimplantation embryonic development, however, remain unknown. Our results showed that the transcripts and protein of WDR5 exhibited stage-specific expression pattern in porcine early embryos. Moreover, blastocyst rate and total cell number per blastocyst were reduced by RNAi-mediated silencing of WDR5 or pharmacological inhibition of WDR5. Knockdown of WDR5 also disturbed the expression of several pluripotency genes. Interestingly, tri-methylation of H3K4 (H3K4me3) level was dramatically increased by WDR5 depletion. Further analysis revealed that loss of MLL3 phenocopied WDR5 knockdown, triggering increased H3K4me3 level. Simultaneously, WDR5 depletion significantly decreased the levels of histone H4 lysine 16 acetylation (H4K16ac) and its writer males absent on the first (MOF). Last but not least, WDR5 knockdown induced DNA damage and DNA repair defects during porcine preimplantation development. Taken together, results of described studies establish that WDR5 plays a significant role in porcine preimplantation embryos probably through regulating key epigenetic modifications and genome integrity.
authors.affiliation: Anhui Provincial Laboratory of Local Livestock and Poultry Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui, China.|Key Laboratory of Embryo Development and Reproduction Regulation of Anhui Province, College of Biological and Food Engineering, Fuyang Normal University, Fuyang, Anhui, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Ding
authors.affiliation: Anhui Provincial Laboratory of Local Livestock and Poultry Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui, China.
authors.forename: Zubing
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Anhui Provincial Laboratory of Local Livestock and Poultry Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui, China.
authors.forename: Renyun
authors.initials: R
authors.lastname: Hong
authors.affiliation: Anhui Provincial Laboratory of Local Livestock and Poultry Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Anhui Provincial Laboratory of Local Livestock and Poultry Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui, China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Anhui Provincial Laboratory of Local Livestock and Poultry Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Luo
authors.affiliation: Anhui Provincial Laboratory of Local Livestock and Poultry Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui, China.
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Anhui Provincial Laboratory of Local Livestock and Poultry Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Huang
authors.affiliation: Key Laboratory of Embryo Development and Reproduction Regulation of Anhui Province, College of Biological and Food Engineering, Fuyang Normal University, Fuyang, Anhui, China.
authors.forename: Wenyong
authors.initials: W
authors.lastname: Li
authors.affiliation: Laboratory of Mammalian Molecular Embryology, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Anhui Provincial Laboratory of Local Livestock and Poultry Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui, China.
authors.forename: Yunhai
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism*; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D055785:Gene Knockdown Techniques; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013552:Swine / Q000196:embryology*; D059467:Transcriptome
chemical_list: D012333:RNA, Messenger; D011495:Histone-Lysine N-Methyltransferase
keywords: DNA damage; H3K4me3; H4K16ac; WDR5; embryo; pig