The Mi-2 nucleosome-remodeling protein LET-418 is targeted via LIN-1/ETS to the promoter of lin-39/Hox during vulval development in C. elegans.
The fate of the vulval cells in Caenorhabditis elegans is specified, at least in part, through a highly conserved RTK/Ras mediated signaling cascade that negatively regulates the activity of the ETS-like transcription factor LIN-1. The Hox gene lin-39 functions downstream of both, the LIN-3/RTK/Ras pathway and LIN-1 and plays a pivotal role in controlling vulva cell competence and induction. Here we show that LET-418, a C. elegans ortholog of the human NuRD component Mi-2, negatively modulates the activity of lin-39. LET-418 interacts in vivo with specific regions in the promoter of lin-39 and this interaction depends on LIN-1. Our data provide evidence for a model in which LIN-1 recruits LET-418/Mi-2 as co-repressor to the promoter of lin-39, thereby restricting its activity to the basal levels required in the vulva precursor cells (VPCs) for normal vulval development. Thus, our data suggest that the interaction between LIN-1 and LET-418/Mi-2 may link RTK/Ras signaling with chromatin remodeling and gene expression.
Guerry
Frédéric
F
Department of Biology, University of Fribourg, Chemin du Musée 10, CH-1700 Fribourg, Switzerland.
Marti
Claude-Olivier
CO
Zhang
Yue
Y
Moroni
Paolo S
PS
Jaquiéry
Emilie
E
Müller
Fritz
F
D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000502:physiology*; D008957:Models, Genetic; D009154:Mutation; D009707:Nucleosomes / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D014157:Transcription Factors / Q000378:metabolism*; D014844:Vulva / Q000196:embryology*
D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C521495:LET-418 protein, C elegans; C097533:Lin-1 protein, C elegans; D009707:Nucleosomes; D014157:Transcription Factors; C108673:lin-39 protein, C elegans