Chromatin targeting of the RNF12/RLIM E3 ubiquitin ligase controls transcriptional responses.
Life Sci Alliance
; 7(3)2024 03.
Article
em En
| MEDLINE
| ID: mdl-38199845
ABSTRACT
Protein ubiquitylation regulates key biological processes including transcription. This is exemplified by the E3 ubiquitin ligase RNF12/RLIM, which controls developmental gene expression by ubiquitylating the REX1 transcription factor and is mutated in an X-linked intellectual disability disorder. However, the precise mechanisms by which ubiquitylation drives specific transcriptional responses are not known. Here, we show that RNF12 is recruited to specific genomic locations via a consensus sequence motif, which enables co-localisation with REX1 substrate at gene promoters. Surprisingly, RNF12 chromatin recruitment is achieved via a non-catalytic basic region and comprises a previously unappreciated N-terminal autoinhibitory mechanism. Furthermore, RNF12 chromatin targeting is critical for REX1 ubiquitylation and downstream RNF12-dependent gene regulation. Our results demonstrate a key role for chromatin in regulation of the RNF12-REX1 axis and provide insight into mechanisms by which protein ubiquitylation enables programming of gene expression.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromatina
/
Deficiência Intelectual
Limite:
Humans
Idioma:
En
Revista:
Life Sci Alliance
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Reino Unido