Sumoylation of the SOX10 transcription factor regulates its transcriptional activity.
SRY-related HMG box-containing factor 10 (SOX10) is a transcription factor essential for neural crest development and differentiation, and involved in Waardenburg syndrome type IV and PCWH syndrome. Here we show that the SOX10 protein is modified by sumoylation, a highly dynamic post-translational modification that affects stability, activity and localisation of some specific transcription factors. Three sumoylation consensus sites were found in the SOX10 protein, all of them are functional and modulate SOX10 activity. Sumoylation does not affect SOX10 sub-cellular localisation, but represses its transcriptional activity on two of its target genes, GJB1 and MITF, and modulates its synergy with its cofactors EGR2 and PAX3 on these promoters.
INSERM U654, Bases Moléculaires et Cellulaires des Maladies Génétiques, France.
Mathilde
M
Girard
Michel
M
Goossens
D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000737:chemistry; D017630:Connexins / Q000235:genetics; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051767:Early Growth Response Protein 2 / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006609:High Mobility Group Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics; D008969:Molecular Sequence Data; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D055757:SOXE Transcription Factors; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*; D000097002:Gap Junction beta-1 Protein; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D017630:Connexins; D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; D006609:High Mobility Group Proteins; D051739:Microphthalmia-Associated Transcription Factor; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D055757:SOXE Transcription Factors; D014157:Transcription Factors; D044763:Ubiquitin-Conjugating Enzymes; D000097002:Gap Junction beta-1 Protein; D000098843:Ubiquitin-Conjugating Enzyme UBC9; C497326:EGR2 protein, human; C489409:PAX3 protein, human; C527923:SOX10 protein, human