2021年第48卷第2期目录
|
|
封面故事:小鼠第一次造血发生在胚胎卵黄囊的血岛上. Ash2l是H3K4甲基转移酶MLL/SET1重要
组分之一,通过可变启动子的选择,该基因编码两种亚型(Ash2-1和Ash2-2),但其发育中的功能
仍不清楚. 本论文利用基因敲除小鼠探讨了Ash2l在卵黄囊造血中的作用和分子机制. Ash2-1基因敲
除导致胚胎发育停滞在胚胎期9.5~10.5,而Ash2-2基因敲除小鼠的胚胎发育基本正常. 胚胎期9.5的
Ash2-1敲除胚胎卵黄囊上血管和造血发育明显异常;红细胞发育和成熟、血管发生和形成相关基因
表达明显下调;一些表达下调基因启动子区的H3K4me3修饰水平明显下降. 上述结果表明,Ash2l-1
在小鼠卵黄囊早期造血和血管形成中必不可少,它可能是通过调控关键基因启动子区H3K4me3修
饰水平控制其表达,进而在相关过程中行使重要功能. 本研究揭示了Ash2l在小鼠早期胚胎发育过程
中的新功能和潜在作用机制,促进了哺乳动物早期造血分子调控的理解.
(王晓晴,卢绪坤,向云龙,李磊. Ash2l-1调控小鼠卵黄囊早期造血,本期第192~203 页)
Cover Story:Ash2l promotes H3K4 trimethylation levels through methyltransferase MLL/SET1 complex, which is
essential for mouse embryonic development. Ash2l have two isoforms (Ash2l-1 and Ash2l-2) through alternative
promoter usage in mouse. However, the mechanism of this gene in mouse embryonic development and the
function of different isoforms remain unknown. In this study, we used CRISPR/Cas9 technology to specifically
disrupt Ash2l-1 in mice and investigated the role of Ash2l-1 in mouse early embryonic development. Disruption of
Ash2l-1 resulted in embryonic lethality at E9.5-10.5. Particularly, E9.5 Ash2l-1-deficient embryos exhibited
severe growth defects, including developmental defects of yolk sac. Gene expression profiling showed that Ash2l-
1 deficiency affected the expression of specific genes involved in erythropoiesis and vascular formation.
CUT&RUN analysis showed that H3K4me3 levels of the promoter of some specific genes involved in
erythropoiesis and vascular formation was down-regulated. Taken together, these results indicate that Ash2l-1
regulates gene expression through H3K4me3 and plays an essential role in the early hematopoiesis of mouse yolk
sacs.
|
综述与专论
研究报告
技术与方法
|
|