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Journal Articles Science Year : 2021

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

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Abstract

The Rett syndrome protein MeCP2 was described as a methyl-CpG-binding protein, but its exact function remains unknown. Here we show that mouse 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 considerably 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.
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Dates and versions

inserm-03376640 , version 1 (13-10-2021)

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Abdulkhaleg Ibrahim, Christophe Papin, Kareem Mohideen-Abdul, Stéphanie Le Gras, Isabelle Stoll, et al.. MeCP2 is a microsatellite binding protein that protects CA repeats from nucleosome invasion. Science, 2021, 372 (6549), ⟨10.1126/science.abd5581⟩. ⟨inserm-03376640⟩
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