| First Author | Szanto A | Year | 2021 |
| Journal | Genes Dev | Volume | 35 |
| Issue | 13-14 | Pages | 1035-1054 |
| PubMed ID | 34168040 | Mgi Jnum | J:317031 |
| Mgi Id | MGI:6842887 | Doi | 10.1101/gad.337592.120 |
| Citation | Szanto A, et al. (2021) A disproportionate impact of G9a methyltransferase deficiency on the X chromosome. Genes Dev 35(13-14):1035-1054 |
| abstractText | G9a is a histone methyltransferase responsible for the dimethylation of histone H3 at lysine 9 (H3K9me2). G9a plays key roles in transcriptional silencing of developmentally regulated genes, but its role in X-chromosome inactivation (XCI) has been under debate. Here, we uncover a female-specific function of G9a and demonstrate that deleting G9a has a disproportionate impact on the X chromosome relative to the rest of the genome. G9a deficiency causes a failure of XCI and female-specific hypersensitivity to drug inhibition of H3K9me2. We show that G9a interacts with Tsix and Xist RNAs, and that competitive inhibition of the G9a-RNA interaction recapitulates the XCI defect. During XCI, Xist recruits G9a to silence X-linked genes on the future inactive X. In parallel on the future Xa, Tsix recruits G9a to silence Xist in cis Thus, RNA tethers G9a for allele-specific targeting of the H3K9me2 modification and the G9a-RNA interaction is essential for XCI. |
