Insights into the function of the human P-TEFb component CDK9 in the regulation of chromatin modifications and co-transcriptional mRNA processing.
Cyclin-dependent kinase-9 (CDK9) was originally characterized as a transcription elongation factor which regulates RNA Polymerase II (RNAPII) activity following transcriptional initiation. However, recent evidence from a number of studies have shown that CDK9 plays an important role in regulating not only RNAPII activity but also co-transcriptional histone modification and mRNA processing events such as splicing and 3' end processing. Importantly, our previous work and the work presented here demonstrate that CDK9 functions to guide a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3. This function appears to be dependent upon not only the phosphorylation of the RNA Polymerase II C-terminal domain but also upon other CDK9 targets such as the Suppressor of Ty Homolog-5 (SUPT5H), Negative Elongation Factor-E (NELF-E) and probably the human Rad6 homolog UBE2A. We provide a working model by which CDK9 may control co-transcriptional replication-dependent histone mRNA 3' end processing in an H2Bub1 and H3K4me3-dependent manner and uncover new and important differences between the functions of human CDK9 and its yeast counterparts Ctk1 and Bur1.
Department of Molecular Oncology, Göttingen Center for Molecular Biosciences, University of Göttingen, Göttingen, Germany.
Judith
J
Pirngruber
Andrei
A
Shchebet
Steven A
SA
Johnsen
D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D042863:Cyclin-Dependent Kinase 9 / Q000378:metabolism / Q000502:physiology*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D006657:Histones / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D011494:Protein Kinases / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013045:Species Specificity
C118305:CTDK-I protein complex, S cerevisiae; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9; D018844:Cyclin-Dependent Kinases; C414163:SGV1 protein, S cerevisiae; D012319:RNA Polymerase II