Conversion of the LIN-1 ETS protein of Caenorhabditis elegans from a SUMOylated transcriptional repressor to a phosphorylated transcriptional activator

• Published in: Genetics (Austin) Vol. 199; no. 3; pp. 761 - 775
• Main Authors: Leight, Elizabeth R, Murphy, John T, Fantz, Douglas A, Pepin, Danielle, Schneider, Daniel L, Ratliff, Thomas M, Mohammad, Duaa H, Herman, Michael A, Kornfeld, Kerry
• Format: Journal Article
• Language: English
• Published: United States Genetics Society of America 01-03-2015
• Subjects: Animals; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell cycle; Evolution & development; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Gene expression; Gene Expression Regulation; Investigations; Kinases; Mi-2 Nucleosome Remodeling and Deacetylase Complex - metabolism; Nematodes; Phosphorylation; Placenta; Repressor Proteins - genetics; Repressor Proteins - metabolism; RNA-protein interactions; Sumoylation; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Two-Hybrid System Techniques; Ubiquitin-Conjugating Enzymes - metabolism; Vulva - physiology; SUMO; LIN-1; transcription; vulval development; chromatin; ETS
• ISSN: 1943-2631; 0016-6731; 1943-2631
• DOI: 10.1534/genetics.114.172668

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.