WDR82, a key epigenetics-related factor, plays a crucial role in normal early embryonic development in mice.
Epigenetic regulation is considered one of the most important mechanisms by which changes in gene expression occur without changes in the underlying DNA sequence. More and more studies have shown that this kind of regulation plays a very important role during the process of early embryonic development. Methylation of histones is a special process in epigenetic regulations that plays a dual role: some activate gene expression, while some inhibit it; trimethylation of histone 3 lysine 4 has been shown to be a marker of gene expression activation. Previous research has led us to focus on the role of WDR82, which has been shown to recognize a subunit in the methyltransferases complex that catalyzes H3K4me3 in early embryonic development. Although it has been shown that a defect in WDR82 causes dysfunction of SETD1A/SETD1B and results in loss of H3K4me3 in human cell lines, the exact role of WDR82 in the methyltransferases complex during early embryonic development is not clear. Our study has shown that a defect in WDR82 causes dysfunction of SETD1A/SETD1B and affects the normal H3K4me3 status in the transcription start region of POU5F1, which then causes the down-regulation of POU5F1 as well as its downstream factors STAT3/BIRC5, which are responsible for the extremely high apoptotic rates of blastocysts. Finally, the result of a blocked WDR82 consists of stunted embryonic development and death. Thus, WDR82 can be considered a key epigenetic regulation-related factor crucial in the normal growth and development of embryos.
Department of Histology and Embryology, Nanjing Medical University, Nanjing, People's Republic of China.
Ye
Y
Bi
Zhuo
Z
Lv
Ying
Y
Wang
Tang
T
Hai
Ran
R
Huo
Zuomin
Z
Zhou
Qi
Q
Zhou
Jiahao
J
Sha
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D020964:Embryo Loss / Q000235:genetics / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics* / Q000502:physiology*; D044127:Epigenesis, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D009865:Oocytes / Q000378:metabolism; D011247:Pregnancy; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015053:Zygote / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D017931:DNA Primers; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C571258:Wdr82 protein, mouse; D011495:Histone-Lysine N-Methyltransferase