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

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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
Issue number3
Publication statusPublished - 1 Mar 2024

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Publisher Copyright: © 2024 Espejo-Serrano et al.


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