| The methylation modification of H3K4 promotes gene expression,and which is mainly accomplished by the methyltransferase MLL/SET1 family protein.The MLL/SET1 family protein contains six protein complexes in mammals:MLL1/MLL,MLL2,MLL3,MLL4,SET1A and SET1B.The six protein complexes share four common core subunits:WDR5,RBBP5,ASH2L,and DPY30,collectively called WRAD.The main role of ASH2L is to promote the trimethylation modification of H3K4.In mice,Ash2l have two different mRNA variants due to the alternative promoter usage,which were further translated into two protein isoforms of different lengths:ASH2L-1 and ASH2L-2.It was mainly stated in this paper that when Ash2l-1 was knockout,mouse embryos died at E9.5-E10.5.Abnormal organ development and yolk sac development were observed in Ash2l-1-/-embryo of E9.5,Ash2l-1-deficient embryos exhibited severe growth defects,including developmental defects of the vascular and hematopoietic on the yolk sac.RNA sequencing of E8.5 yolk sac showed that the expression of specific genes involved in erythropoiesis and vascular formation were significantly down-regulated.In vitro cell experiments,it was found that Ash2l-1 deletion did not affect the proliferation and pluripotency of mouse embryonic stem cells,but affected the differentiation of embryonic stem cells into embryoids and teratomas.In Ash2l-1-/-embryoids,the proportion of beating clone decreased,and the expression of erythrocyte and angiogenesis related genes decreased significantly.The morphology of teratomas formed by Ash2l-1-/-embryonic stem cells decreased significantly,and the number of erythrocytes derived from mesoderm also decreased significantly.Significant downregulation of H3K4me3 levels was found in Ash2l-1-deficient embryo yolk sacs and embryoid bodys.Combined with CUT&RUN results of H3K4me3 on yolk sac,Ash2l-1 may regulate the expression of genes related to erythropoiesis and maturation,angiogenesis and formation through the modification of H3K4me3 in the key gene promoters region. |
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