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31 March 2017 WDR5 in porcine preimplantation embryos: expression, regulation of epigenetic modifications and requirement for early development
Biao Ding, Zubing Cao, Renyun Hong, Hui Li, Xiaoyuan Zuo, Lei Luo, Yunsheng Li, Weiping Huang, Wenyong Li, Kun Zhang, Yunhai Zhang
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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.

Summary Sentence

WDR5 participates in the regulation of porcine embryonic development, likely mediated by regulation of epigenetic modifications (H3K4me3 and H4K16ac) and genome integrity.

© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please journals.permissions@oup.com
Biao Ding, Zubing Cao, Renyun Hong, Hui Li, Xiaoyuan Zuo, Lei Luo, Yunsheng Li, Weiping Huang, Wenyong Li, Kun Zhang, and Yunhai Zhang "WDR5 in porcine preimplantation embryos: expression, regulation of epigenetic modifications and requirement for early development," Biology of Reproduction 96(4), 758-771, (31 March 2017). https://doi.org/10.1093/biolre/iox020
Received: 2 December 2016; Accepted: 29 March 2017; Published: 31 March 2017
JOURNAL ARTICLE
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