A disproportionate impact of G9a methyltransferase deficiency on the X chromosome

Attila Szanto, Rodrigo Aguilar, Barry Kesner, Roy Blum, Danni Wang, Catherine Cifuentes-Rojas, Brian C. del Rosario, Katalin Kis-Toth, Jeannie T. Lee

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

1 Cita (Scopus)

Resumen

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 showthat 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.

Idioma originalInglés
Páginas (desde-hasta)1035-1054
Número de páginas20
PublicaciónGenes and Development
Volumen35
N.º13
DOI
EstadoPublicada - 1 jul. 2021
Publicado de forma externa

Áreas temáticas de ASJC Scopus

  • Genética
  • Biología del desarrollo

Huella

Profundice en los temas de investigación de 'A disproportionate impact of G9a methyltransferase deficiency on the X chromosome'. En conjunto forman una huella única.

Citar esto