Sumoylation of LIN-1 promotes transcriptional repression and inhibition of vulval cell fates.
The LIN-1 ETS transcription factor inhibits vulval cell fates during Caenorhabditis elegans development. We demonstrate that LIN-1 interacts with UBC-9, a small ubiquitin-related modifier (SUMO) conjugating enzyme. This interaction is mediated by two consensus sumoylation motifs in LIN-1. Biochemical studies showed that LIN-1 is covalently modified by SUMO-1. ubc-9 and smo-1, the gene encoding SUMO-1, inhibit vulval cell fates and function at the level of lin-1, indicating that sumoylation promotes LIN-1 inhibition of vulval cell fates. Sumoylation of LIN-1 promoted transcriptional repression and mediated an interaction with MEP-1, a protein previously shown to associate with the nucleosome remodeling and histone deacetylation (NuRD) transcriptional repression complex. Genetic studies showed that mep-1 inhibits vulval cell fates and functions at the level of lin-1. We propose that sumoylation of LIN-1 mediates an interaction with MEP-1 that contributes to transcriptional repression of genes that promote vulval cell fates. These studies identify a molecular mechanism for SUMO-mediated transcriptional repression.
Leight
Elizabeth R
ER
Department of Molecular Biology and Pharmacology Washington University School of Medicine, St Louis, MO 63110, USA.
Glossip
Danielle
D
Kornfeld
Kerry
K
D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002460:Cell Line; D019070:Cell Lineage; D002843:Chromatin / Q000378:metabolism; D005260:Female; D017930:Genes, Reporter; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D025842:SUMO-1 Protein / Q000378:metabolism / Q000502:physiology*; D012441:Saccharomyces cerevisiae; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D014844:Vulva / Q000196:embryology*
D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; C097533:Lin-1 protein, C elegans; C459463:MEP-1 protein, C elegans; D025842:SUMO-1 Protein; D014157:Transcription Factors