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.
Author(s):
PubMed:
38199845
Espejo-Serrano C, Aitken C, Tan BF, May DG, Chrisopulos RJ, Roux KJ, Demmers JA, Mackintosh SG, Gribnau J, Bustos F, Gontan C, Findlay GM