title: Conversion of the LIN-1 ETS protein of Caenorhabditis elegans from a SUMOylated transcriptional repressor to a phosphorylated transcriptional activator.
abstract: The LIN-1 ETS transcription factor plays a pivotal role in controlling cell fate decisions during development of the Caenorhabditis elegans vulva. Prior to activation of the RTK/Ras/ERK-signaling pathway, LIN-1 functions as a SUMOylated transcriptional repressor that inhibits vulval cell fate. Here we demonstrate using the yeast two-hybrid system that SUMOylation of LIN-1 mediates interactions with a protein predicted to be involved in transcriptional repression: the RAD-26 Mi-2β/CHD4 component of the nucleosome remodeling and histone deacetylation (NuRD) transcriptional repression complex. Genetic studies indicated that rad-26 functions to inhibit vulval cell fates in worms. Using the yeast two-hybrid system, we showed that the EGL-27/MTA1 component of the NuRD complex binds the carboxy-terminus of LIN-1 independently of LIN-1 SUMOylation. EGL-27 also binds UBC-9, an enzyme involved in SUMOylation, and MEP-1, a zinc-finger protein previously shown to bind LIN-1. Genetic studies indicate that egl-27 inhibits vulval cell fates in worms. These results suggest that LIN-1 recruits multiple proteins that repress transcription via both the SUMOylated amino-terminus and the unSUMOylated carboxy-terminus. Assays in cultured cells showed that the carboxy-terminus of LIN-1 was converted to a potent transcriptional activator in response to active ERK. We propose a model in which LIN-1 recruits multiple transcriptional repressors to inhibit the 1° vulval cell fate, and phosphorylation by ERK converts LIN-1 to a transcriptional activator that promotes the 1° vulval cell fate.
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Leight
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: John T
authors.initials: JT
authors.lastname: Murphy
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Fantz
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Danielle
authors.initials: D
authors.lastname: Pepin
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Schneider
authors.affiliation: Division of Biology, Kansas State University, Manhattan, Kansas 66506.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Ratliff
authors.affiliation: Division of Biology, Kansas State University, Manhattan, Kansas 66506.
authors.forename: Duaa H
authors.initials: DH
authors.lastname: Mohammad
authors.affiliation: Division of Biology, Kansas State University, Manhattan, Kansas 66506.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Herman
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri 63110 kornfeld@wustl.edu.
authors.forename: Kerry
authors.initials: K
authors.lastname: Kornfeld
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism; D010766:Phosphorylation; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D014844:Vulva / Q000502:physiology; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D029742:Caenorhabditis elegans Proteins; C097533:Lin-1 protein, C elegans; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D044763:Ubiquitin-Conjugating Enzymes; D048049:Extracellular Signal-Regulated MAP Kinases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D000098843:Ubiquitin-Conjugating Enzyme UBC9
keywords: ETS; LIN-1; SUMO; chromatin; transcription; vulval development