BACKGROUND: The Tousled kinases comprise an evolutionarily conserved family of proteins that have been previously implicated in chromatin remodeling, DNA replication, and DNA repair. Here, we used RNA mediated interference (RNAi) to determine the function of the C. elegans Tousled kinase (TLK-1) during embryonic development. RESULTS: TLK-1-deficient embryos arrested with a phenotype reminiscent of embryos that are broadly defective in transcription, and the expression of several reporter genes was dramatically reduced in tlk-1(RNAi) embryos. Furthermore, posttranslational modifications of RNA polymerase II (RNAPII) and histone H3 that have been correlated with transcription elongation, phosphorylation of the RNAPII CTD at Serine 2, and methylation of histone H3 at Lysine 36 were found at significantly reduced levels in tlk-1(RNAi) embryos as compared to wild-type. CONCLUSIONS: These results reveal a surprising requirement for a Tousled-like kinase in transcriptional regulation during development, likely during the elongation phase. In addition, our results confirm that the link between RNAPII phosphorylation and histone H3 methylation previously observed in budding yeast is functionally conserved in metazoans.
BACKGROUND: The Tousled kinases comprise an evolutionarily conserved family of proteins that have been previously implicated in chromatin remodeling, DNA replication, and DNA repair. Here, we used RNA mediated interference (RNAi) to determine the function of the C. elegans Tousled kinase (TLK-1) during embryonic development. RESULTS:TLK-1-deficient embryos arrested with a phenotype reminiscent of embryos that are broadly defective in transcription, and the expression of several reporter genes was dramatically reduced in tlk-1(RNAi) embryos. Furthermore, posttranslational modifications of RNA polymerase II (RNAPII) and histone H3 that have been correlated with transcription elongation, phosphorylation of the RNAPII CTD at Serine 2, and methylation of histone H3 at Lysine 36 were found at significantly reduced levels in tlk-1(RNAi) embryos as compared to wild-type. CONCLUSIONS: These results reveal a surprising requirement for a Tousled-like kinase in transcriptional regulation during development, likely during the elongation phase. In addition, our results confirm that the link between RNAPII phosphorylation and histone H3 methylation previously observed in budding yeast is functionally conserved in metazoans.
Authors: Laurel B Bender; Jinkyo Suh; Coleen R Carroll; Youyi Fong; Ian M Fingerman; Scott D Briggs; Ru Cao; Yi Zhang; Valerie Reinke; Susan Strome Journal: Development Date: 2006-10 Impact factor: 6.868
Authors: Stephanie A Morris; Yoichiro Shibata; Ken-ichi Noma; Yuko Tsukamoto; Erin Warren; Brenda Temple; Shiv I S Grewal; Brian D Strahl Journal: Eukaryot Cell Date: 2005-08