Asymmetric cell division is one of the fundamental mechanisms to produce cell diversity. It was reported that components of the transcriptional Mediator complex, DPY-22/MED12 and LET-19/MED13, are required for asymmetric cell division of the T cell in C.elegans. By screening for mutants with abnormal T cell lineage, we isolated mutants of the
cdk-8/CDK8 and
cic-1/CyclinC genes that encode other components of the Mediator complex. In addition to the T cell lineage,
dpy-22,
let-19,
cdk-8 and
cic-1 are also required for the asymmetric cell fates in V5.p lineage. These results indicate that these four genes are required for transcriptional regulation during multiple asymmetric cell divisions. The Mediator complex is a large multisubunit complex that consists of four modules. It is known that SRB8/MED12, SRB9/MED13, SRB10/CDK8, and SRB11/CyclinC form module in yeast. Phosphorylation by CDK8 is an important output from this module. CDK8/SRB10 phosphorylates PolII, CyclinH or DNA-binding transcription factors to repress transcription in mammal and yeast. CyclinC/SRB11 is known as a binding partner of CDK8/SRB10. But, the function of SRB8/MED12/DPY-22 and SRB9/MED13/LET-19 is not clear yet. However, it is expected that MED12 and MED13 may regulate the kinase activity of CDK8 since they are components of the same module. Actually, analyses of four mutants,
dpy-22,
let-19,
cdk-8 and
cic-1, indicates that DPY-22 and LET-19 have antagonistic role to CDK-8 to regulate
tlp-1 expression in the T cell lineage.
tlp-1::gfp expression is higher in posterior daughter of the T cell than in anterior daughter in wild-type animal. In
dpy-22 or
let-19 mutants, intense
tlp-1 expression is observed in the both daughter cells. In contrast,
tlp-1::gfp expression was weak in those of
cdk-8 or
cic-1 mutants. These results indicate that
cdk-8 and
cic-1 is required for up-regulation of the
tlp-1 expression but
dpy-22 and
let-19 is required for down-regulation. DPY-22 and LET-19 may be required for the repression of the CDK-8 activity. In addition to the antagonistic role, the following results indicate that LET-19 and DPY-22 appear to have CDK-8-independent roles.
dpy-22 or
let-19 mutants showed stronger defect in the V5.p lineage and in the vulva (Multivulva) than putative
cdk-8 or
cic-1 null mutant. In addition,
cdk-8 or
cic-1 null mutants are fertile but
let-19 or
dpy-22 mutants were sterile or semi-sterile respectively. Together with the result of
tlp-1 expression, DPY-22 and LET-19 may have complex function to regulate the multiple output from the module containing these proteins.