| First Author | Ibrahim A | Year | 2021 |
| Journal | Science | Volume | 372 |
| Issue | 6549 | PubMed ID | 34324427 |
| Mgi Jnum | J:311159 | Mgi Id | MGI:6766086 |
| Doi | 10.1126/science.abd5581 | Citation | Ibrahim A, et al. (2021) MeCP2 is a microsatellite binding protein that protects CA repeats from nucleosome invasion. Science 372(6549) |
| abstractText | 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(133), 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. |
