Chromatin targeting of the RNF12/RLIM E3 ubiquitin ligase controls transcriptional responses

Carmen Espejo-Serrano, Catriona Aitken, Beatrice F. Tan, Danielle G. May, Rachel J. Chrisopulos, Kyle J. Roux, Jeroen Aa Demmers, Samuel G. Mackintosh, Joost Gribnau, Francisco Bustos, Cristina Gontan, Greg M. Findlay

Research output: Contribution to journalArticleAcademicpeer-review

4 Downloads (Pure)

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.

Original languageEnglish
JournalLife Science Alliance
Volume7
Issue number3
DOIs
Publication statusPublished - 1 Mar 2024

Bibliographical note

Publisher Copyright: © 2024 Espejo-Serrano et al.

Fingerprint

Dive into the research topics of 'Chromatin targeting of the RNF12/RLIM E3 ubiquitin ligase controls transcriptional responses'. Together they form a unique fingerprint.

Cite this