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[交流] 【分享】WDR82在早期胚胎发育中的重要作用

WDR82, a key epigenetics related factor, plays crucial role in normal early embryonic development
WDR82在早期胚胎发育中的重要作用
Jiahao Sha Biolreprod December 1, 2010
摘要：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 duel role, some activate the gene
expression while some inhibit; tri-methylation of histone 3 lysine 4 has been shown to
be a marker of gene expression activation. Previous researches have 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.
摘要
1：表观遗传学调控，是在DNA序列没有变化的情况下，对基因表达进行调控的一种重要手段。我们认为，该种调控在胚胎的早期发育中起着重要作用。
2：组氨酸的甲基化作为其中的一种，可以启动一些基因的表达，也可以沉默一些基因的表达；H3K4me3，对组蛋白3的4号赖氨酸位点进行三重甲基化作用，是基因表达活化的一种标志性作用。
3：前期研究表示，WDR82作为甲基化转移酶复合体的组件之一，参与早期胚胎发育中，H3K4me3作用的催化。虽然，已经研究出WDR82的缺失可以引起SETD1A/SETD1B 的功能紊乱及在人类细胞水平上H3K4me3的缺失，但其在甲基化转移酶复合体中的具体相关作用仍不明了。
4：本实验研究表明：WDR82的缺失导致SETD1A/SETD1B功能紊乱；通过影响pou5f1的转录，从而影响其调控的下游因子，如STAR3/BIRC5，导致了胚胎发育阻滞及死亡。所以，表观遗传调控的相关因子，WDR82，对胚胎的早期发育及分化起着重要作用。
更多资料请查看www.bioknow.cn

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