SNAP output for PDB entry 6yww [SNAP web server]

PDB-id

6yww; SNAP-derived features in text and JSON formats; DNAproDB

Class

DNA binding protein

Method

X-ray (2.102 Å)

Summary

Mecp2 is a microsatellite binding protein that protects ca repeats from nucleosome invasion

Reference

Ibrahim A, Papin C, Mohideen-Abdul K, Le Gras S, Stoll I, Bronner C, Dimitrov S, Klaholz BP, Hamiche A (2021): "MeCP2 is a microsatellite binding protein that protects CA repeats from nucleosome invasion." Science, 372. doi: 10.1126/science.abd5581.

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.