6YWW

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

Summary for 6YWW

• Entry DOI: 10.2210/pdb6yww/pdb
• Descriptor: Truncated methyl CpG binding protein 2 transcript 1, DNA/RNA (5'-D(*TP*CP*TP*GP*CP*AP*CP*A)-R(P*(5HC))-D(P*AP*CP*AP*CP*AP*AP*TP*TP*AP*TP*A)-3'), DNA (5'-D(*AP*TP*AP*TP*AP*AP*TP*TP*GP*TP*GP*TP*GP*TP*GP*TP*GP*CP*AP*G)-3'), ... (4 entities in total)
• Functional Keywords: rett syndrome, microsatellite dna, dna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 23736.90

Authors

Ibrahim, A.,Papin, C.,Mohideen-Abdul, K.,Gras, S.L.,Stoll, I.,Bronner, C.,Dimitrov, S.,Klaholz, B.P.,Hamiche, A. (deposition date: 2020-04-30, release date: 2021-06-16, Last modification date: 2024-01-24)

Primary citation

Ibrahim, A.,Papin, C.,Mohideen-Abdul, K.,Le Gras, S.,Stoll, I.,Bronner, C.,Dimitrov, S.,Klaholz, B.P.,Hamiche, A.
MeCP2 is a microsatellite binding protein that protects CA repeats from nucleosome invasion.
Science, 372:-, 2021

PubMed 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 Arg, 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.

PubMed: 34324427
DOI: 10.1126/science.abd5581

Experimental method

X-RAY DIFFRACTION (2.102 Å)