Conversion of the LIN-1 ETS protein of C. elegans from a sumoylated transcriptional repressor to a phosphorylated transcriptional activator

ARTICLE SUMMARY 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 the primary vulval cell fate. Here we demonstrate that LIN-1 binds two proteins predicted to repress transcription: RAD-26 binds the SUMOylated amino-terminus and EGL-27 binds the unSUMOylated carboxy terminus. We propose a model in which LIN-1 recruits multiple transcriptional repressors to inhibit the primary vulval cell fate, and phosphorylation by ERK converts LIN-1 to a transcriptional activator that promotes the primary vulval cell fate. 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 fates. 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 independent 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 indicated 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. Leight et al.