Components of the transcriptional Mediator complex are required for asymmetric cell division in C. elegans.
Asymmetric cell division is a fundamental process that produces cellular diversity during development. In C. elegans, the Wnt signaling pathway regulates the asymmetric divisions of a number of cells including the T blast cell. We found that the let-19 and dpy-22 mutants have defects in their T-cell lineage, and lineage analyses showed that the defects were caused by disruption in the asymmetry of the T-cell division. We found that let-19 and dpy-22 encode homologs of the human proteins MED13/TRAP240 and MED12/TRAP230, respectively, which are components of the Mediator complex. Mediator is a multi-component complex that can regulate transcription by transducing the signals between activators and RNA polymerase in vitro. We also showed that LET-19 and DPY-22 form a complex in vivo with other components of Mediator, SUR-2/MED23 and LET-425/MED6. In the let-19 and dpy-22 mutants, tlp-1, which is normally expressed asymmetrically between the T-cell daughters through the function of the Wnt pathway, was expressed symmetrically in both daughter cells. Furthermore, we found that the let-19 and dpy-22 mutants were defective in the fusion of the Pn.p cell, a process that is regulated by bar-1/beta-catenin. Ectopic cell fusion in bar-1 mutants was suppressed by the let-19 or dpy-22 mutations, while defective cell fusion in let-19 mutants was suppressed by lin-39/Hox mutations, suggesting that let-19 and dpy-22 repress the transcription of lin-39. These results suggest that LET-19 and DPY-22 in the Mediator complex repress the transcription of Wnt target genes.
Yoda
Akinori
A
Division of Neuroanatomy, Osaka University Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan.
Kouike
Hiroko
H
Okano
Hideyuki
H
Sawa
Hitoshi
H
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division / Q000502:physiology*; D002459:Cell Fusion; D019070:Cell Lineage / Q000235:genetics; D003001:Cloning, Molecular; D040461:Gene Components; D018507:Gene Expression Regulation, Developmental; D047468:Immunoprecipitation; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D046911:Macromolecular Substances / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D051153:Wnt Proteins
D029742:Caenorhabditis elegans Proteins; D036341:Intercellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; C451879:TLP-1 protein, Caenorhabditis elegans; D014157:Transcription Factors; D051153:Wnt Proteins; C413707:dpy-22 protein, C elegans; C488667:let-19 protein, C elegans