生物
异染色质
组蛋白甲基转移酶
组蛋白H3
EZH2型
端粒
异染色质蛋白1
染色质
组蛋白
表观遗传学
甲基转移酶
染色质免疫沉淀
甲基化
遗传学
黑腹果蝇
组蛋白密码
细胞生物学
DNA
核小体
基因表达
基因
发起人
作者
Marta García‐Cao,Roderick J. O’Sullivan,Antoine H.F.M. Peters,Thomas Jenuwein,Marı́a A. Blasco
出处
期刊:Nature Genetics
[Springer Nature]
日期:2003-12-14
卷期号:36 (1): 94-99
被引量:534
摘要
Telomeres are capping structures at the ends of eukaryotic chromosomes composed of TTAGGG repeats bound to an array of specialized proteins. Telomeres are heterochromatic regions. Yeast and flies with defects in activities that modify the state of chromatin also have abnormal telomere function, but the putative role of chromatin-modifying activities in regulating telomeres in mammals is unknown. Here we report on telomere length and function in mice null with respect to both the histone methyltransferases (HMTases) Suv39h1 and Suv39h2 (called SUV39DN mice). Suv39h1 and Suv39h2 govern methylation of histone H3 Lys9 (H3-Lys9) in heterochromatic regions. We show that primary cells derived from SUV39DN mice have abnormally long telomeres relative to wild-type controls. Using chromatin immunoprecipitation (ChIP) analysis, we found that telomeres were enriched in di- and trimethylated H3-Lys9 but that telomeres of SUV39DN cells had less dimethylated and trimethylated H3-Lys9 but more monomethylated H3-Lys9. Concomitant with the decrease in H3-Lys9 methylation, telomeres in SUV39DN cells had reduced binding of the chromobox proteins Cbx1, Cbx3 and Cbx5, homologs of Drosophila melanogaster heterochromatin protein 1 (HP1). These findings indicate substantial changes in the state of telomeric heterochromatin in SUV39DN cells, which are associated with abnormal telomere elongation. Taken together, the results indicate epigenetic regulation of telomere length in mammals by Suv39h1 and Suv39h2.
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