Godde J S, Kass S U, Hirst M C, Wolffe A P
Laboratory of Molecular Embryology, NICHHD, National Institutes of Health, Bethesda, Maryland 20892-5430, USA.
J Biol Chem. 1996 Oct 4;271(40):24325-8. doi: 10.1074/jbc.271.40.24325.
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.
CGG重复序列的扩增和甲基化与人类脆性X综合征相关。我们研究了CGG重复序列扩增和甲基化对脆性X智力低下基因1（FMR1）上核小体组装和定位的影响。就对组蛋白八聚体的亲和力或重组核小体的定位而言，短的未甲基化CGG重复序列并无特别优势。然而，甲基化后，它们对组蛋白八聚体的亲和力增加，并且一个高度定位的核小体与位于核小体二分体附近的重复序列组装在一起。这些CGG重复序列的扩增消除了甲基化导致的优先核小体组装。因此，这些三联体重复序列的扩增和甲基化可改变染色质的功能组织，这可能导致FMR1基因表达改变和疾病表型。
