Terry Fox Molecular Oncology Group, Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Department of Oncology, McGill University, Montréal, QC, Canada.
Epigenetics. 2013 Feb;8(2):177-83. doi: 10.4161/epi.23416. Epub 2013 Jan 16.
The histone H2A variant H2AZ is an essential chromatin signaling factor. Herein, we report that H2AZ is monomethylated at lysine 7 (H2AZK7me1) by the lysine methyltransferase SETD6. We observed that methylation of H2AZ increased noticeably upon cellular differentiation of mouse embryonic stem cells (mESCs). H2AZK7me1 and the repressive H3K27me3 mark were found near the transcriptional start sites of differentiation marker genes, but were removed upon retinoic acid-induced cellular differentiation. The depletion of Setd6 in mESCs led to cellular differentiation, compromised self-renewal, and poor clonogenicity. These findings demonstrate that mESCs require Setd6 for self-renewal and portray H2AZK7me1 as a marker of cellular differentiation.
组蛋白 H2A 变体 H2AZ 是一种重要的染色质信号因子。在此，我们报告赖氨酸甲基转移酶 SETD6 可使赖氨酸 7 单甲基化组蛋白 H2AZ（H2AZK7me1）。我们观察到，在小鼠胚胎干细胞（mESCs）的细胞分化过程中，H2AZ 的甲基化明显增加。H2AZK7me1 和抑制性 H3K27me3 标记位于分化标记基因的转录起始位点附近，但在维甲酸诱导的细胞分化时被去除。mESCs 中 Setd6 的缺失导致细胞分化、自我更新受损和克隆形成能力差。这些发现表明，mESCs 需要 Setd6 进行自我更新，并将 H2AZK7me1 描绘为细胞分化的标志物。
