| First Author | Nettles SA | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 12 | Pages | 113538 |
| PubMed ID | 38096051 | Mgi Jnum | J:348588 |
| Mgi Id | MGI:7568702 | Doi | 10.1016/j.celrep.2023.113538 |
| Citation | Nettles SA, et al. (2023) MeCP2 represses the activity of topoisomerase IIbeta in long neuronal genes. Cell Rep 42(12):113538 |
| abstractText | A unique signature of neurons is the high expression of the longest genes in the genome. These genes have essential neuronal functions, and disruption of their expression has been implicated in neurological disorders. DNA topoisomerases resolve DNA topological constraints and facilitate neuronal long gene expression. Conversely, the Rett syndrome protein, methyl-CpG-binding protein 2 (MeCP2), can transcriptionally repress long genes. How these factors regulate long genes is not well understood, and whether they interact is not known. Here, we identify and map a functional interaction between MeCP2 and topoisomerase IIbeta (TOP2beta) in mouse neurons. We profile neuronal TOP2beta activity genome wide, detecting enrichment at regulatory regions and gene bodies of long genes, including MeCP2-regulated genes. We show that loss and overexpression of MeCP2 alter TOP2beta activity at MeCP2-regulated genes. These findings uncover a mechanism of TOP2beta inhibition by MeCP2 in neurons and implicate TOP2beta dysregulation in disorders caused by MeCP2 disruption. |
