Tuano Natasha K, Okabe Jun, Ziemann Mark, Cooper Mark E, El-Osta Assam
Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia.
Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia
Nucleic Acids Res. 2016 Nov 2;44(19):9206-9217. doi: 10.1093/nar/gkw621. Epub 2016 Jul 20.
Histone methylation by lysine methyltransferase enzymes regulate the expression of genes implicated in lineage specificity and cellular differentiation. While it is known that Set7 catalyzes mono-methylation of histone and non-histone proteins, the functional importance of this enzyme in stem cell differentiation remains poorly understood. We show Set7 expression is increased during mouse embryonic stem cell (mESC) differentiation and is regulated by the pluripotency factors, Oct4 and Sox2. Transcriptional network analyses reveal smooth muscle (SM) associated genes are subject to Set7-mediated regulation. Furthermore, pharmacological inhibition of Set7 activity confirms this regulation. We observe Set7-mediated modification of serum response factor (SRF) and mono-methylation of histone H4 lysine 4 (H3K4me1) regulate gene expression. We conclude the broad substrate specificity of Set7 serves to control key transcriptional networks in embryonic stem cells.
赖氨酸甲基转移酶催化的组蛋白甲基化可调节与细胞谱系特异性和细胞分化相关的基因表达。虽然已知Set7催化组蛋白和非组蛋白的单甲基化，但该酶在干细胞分化中的功能重要性仍知之甚少。我们发现，Set7在小鼠胚胎干细胞（mESC）分化过程中表达增加，并受多能性因子Oct4和Sox2的调控。转录网络分析显示，与平滑肌（SM）相关的基因受Set7介导的调控。此外，Set7活性的药理学抑制证实了这种调控。我们观察到，Set7介导的血清反应因子（SRF）修饰和组蛋白H4赖氨酸4的单甲基化（H3K4me1）调节基因表达。我们得出结论，Set7广泛的底物特异性有助于控制胚胎干细胞中的关键转录网络。
