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 A. A. Demmers, Samuel G. Mackintosh, Joost Gribnau, Francisco Bustos, Cristina Gontan, Greg M. Findlay (Lead / Corresponding author)

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Abstract

Protein ubiquitylation regulates key biological processes including transcription. This isexemplified by the E3 ubiquitin ligase RNF12/RLIM, which controls developmental geneexpression by ubiquitylating the REX1 transcription factor and is mutated in an X-linkedintellectual disability disorder. However, the precise mechanisms by which ubiquitylationdrives specific transcriptional responses are not known. Here, we show that RNF12 isrecruited to specific genomic locations via a consensus sequence motif, which enables colocalisationwith REX1 substrate at gene promoters. Surprisingly, RNF12 chromatinrecruitment is achieved via a non-catalytic basic region and comprises a previouslyunappreciated N-terminal autoinhibitory mechanism. Furthermore, RNF12 chromatintargeting is critical for REX1 ubiquitylation and downstream RNF12-dependent generegulation. Our results demonstrate a key role for chromatin in regulation of the RNF12-REX1axis and provide insight into mechanisms by which protein ubiquitylation enablesprogramming of gene expression.
Original languageEnglish
Article numbere202302282
Number of pages19
JournalLife Science Alliance
Volume7
Issue number3
Early online date10 Jan 2024
DOIs
Publication statusPublished - Mar 2024

Keywords

  • E3 ubiquitin ligase
  • RNF12/RLIM
  • embryonic stem cells
  • protein ubiquitylation
  • genomic targeting
  • chromatin
  • developmental transcription.

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Health, Toxicology and Mutagenesis
  • Plant Science
  • Ecology

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