A disproportionate impact of G9a methyltransferase deficiency on the X chromosome.
Genes Dev
; 35(13-14): 1035-1054, 2021 07 01.
Article
em En
| MEDLINE
| ID: mdl-34168040
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Histona-Lisina N-Metiltransferase
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Cromossomos Humanos X
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RNA Longo não Codificante
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Antígenos de Histocompatibilidade
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Metiltransferases
Limite:
Female
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Humans
Idioma:
En
Revista:
Genes Dev
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos