Nucleosome assembly on methylated CGG triplet repeats in the Fragile X Mental Retardation gene 1 promoter

被引:74
作者
Godde, JS
Kass, SU
Hirst, MC
Wolffe, AP
机构
[1] NICHHD,LAB MOL EMBRYOL,NIH,BETHESDA,MD 20892
[2] JOHN RADCLIFFE HOSP,INST MOL MED,OXFORD OX3 9D4,ENGLAND
关键词
D O I
10.1074/jbc.271.40.24325
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Expansion and methylation of CGG repeat sequences is associated with Fragile X syndrome in humans. We have examined the consequences of CGG repeat expansion and methylation for nucleosome assembly and positioning on the Fragile X Mental Retardation gene 1 (FMR1) gene. Short unmethylated CGG repeats are not particularly favored in terms of affinity for the histone octamer or for positioning of the reconstituted nucleosome. However, upon methylation their affinity for the histone octamer increases and a highly positioned nucleosome assembles with the repeat sequences found adjacent to the nucleosomal dyad. Expansion of these CGG repeats abolishes the preferential nucleosome assembly due to methylation. Thus, the expansion and methylation of these triplet repeats can alter the functional organization of chromatin, which may contribute to alterations in the expression of the FMR1 gene and the disease phenotype.
引用
收藏
页码:24325 / 24328
页数:4
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