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MeCP2 is a microsatellite binding protein that protects CA repeats from nucleosome invasion

ABSTRACT: MeCP2 is a microsatellite binding protein that protects CA repeats from nucleosome invasion

PROVIDER: PRJNA511390 | ENA |

REPOSITORIES: ENA

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MeCP2 is a microsatellite binding protein that protects CA repeats from nucleosome invasion

Project description:The Rett syndrome protein MeCP2 was described as a methyl-CpG-binding protein, but its exact function remains unknown. Here we show that MeCP2 is a microsatellite binding protein that specifically recognizes hydroxymethylated CA repeats. Depletion of MeCP2 alters chromatin organization of CA repeats and lamina-associated domains and results in nucleosome accumulation on CA repeats and genome-wide transcriptional dysregulation. The structure of MeCP2 in complex with a hydroxymethylated CA repeat reveals a characteristic DNA shape, with significantly modified geometry at the 5-hydroxymethylcytosine, which is recognized specifically by Arg133, a key residue whose mutation causes Rett syndrome. Our work identifies MeCP2 as a microsatellite DNA binding protein that targets the 5hmC-modified CA-rich strand and maintains genome regions nucleosome-free, suggesting a role for MeCP2 dysfunction in Rett syndrome.

2021-06-25 | GSE154111 | GEO

MeCP2 is a microsatellite binding protein that protects CA repeats from nucleosome invasion

2021-06-25 | GSE124240 | GEO