摘要
组蛋白H2A.X第139位丝氨酸磷酸化,形成γ-H2A.X。γ-H2A.X的正确形成对于DNA损伤修复、基因组稳定性和肿瘤发生至关重要,但其形成的机制仍不明确。我们在乳腺癌细胞SKBR3中检测到H2A.X的一种新的修饰方式——第39位酪氨酸残基(Y39)磷酸化,这是国内外首次报道这一修饰。经过一系列内源性和外源性实验证实,H2A.X Y39位点的磷酸化修饰(H2A.X^(Y39ph))是γ-H2A.X形成的必要前提条件。高水平的H2A.X^(Y39ph)能够促进乳腺癌细胞增殖,这一功能依赖于Nanog和Oct4及下游靶基因的转录水平上调。这一新修饰位点的阐明为肿瘤发生和DNA损伤反应中染色质重塑研究提供了新机制。
γ--H2A.X was formed by phosphorylation of the 139th serine in histone H2A.X. Proper formation of γ--H2A.X was critical to DNA damage repair, genome stability and tumorigenesis. However, the mechanism of its formation still remains unclear. We have detected a new modification way of H2A.X in breast cancer cells SKBR3-phosphorylation of the 39^th tyrosine residues (Y39), which was first reported at home and abroad. Through a series of endogenous and exogenous experiments, we known that phosphorylation modification (H2A.XY39ph) of H2A.X Y39 site was a necessary precondition for the formation of γ--H2A.X. High level of H2A.X Y 39 could promote the proliferation of breast cancer cells, and this function relied on Nanog, Oct4 and the up-regulated transcriptional level of downstream target genes. The elucidation of this new modification site provided a new mechanism for the study of chromatin remodeling in tumorigenesis and DNA damage response.
出处
《基因组学与应用生物学》
CAS
CSCD
北大核心
2017年第3期1161-1166,共6页
Genomics and Applied Biology
基金
国家自然科学基金(81302324)资助
关键词
H2A.X
磷酸化
乳腺癌
增殖
H2A.X, Phosphorylation, Breast cancer, Proliferation