CDK9 and H2B Monoubiquitination A Well-Choreographed Dance 英文参考文献.docVIP

Perspective CDK9andH2BMonoubiquitination:AWell- ChoreographedDance StevenA.Johnsen1,2 * 1Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 2Department of Molecular Oncology, University of Go¨ttingen MedicalCenter,Go¨ttingen,Germany Transcriptionalregulationineukaryotes requires the transcriptional machinery to negotiate the complexities of DNA pack- aged into chromatin. Specific modifica- tions ofthecorehistone proteinsserveto regulate transcription and ensure that genes are expressed at the right place and the right time [1]. Not surprisingly, theinteractionbetweenthetranscriptional apparatus and chromatin is a tango in whichthepartnersareinacloseembrace. Cyclin-dependentkinase9(CDK9)andits orthologs control both transcription and transcription-coupledchromatinmodifica- tionsinavarietyofspecies[2,3].Howev- er,themechanismsthatintertwineCDK9 functionwithchromatinappeartobedis- tinct in different organisms. A new man- uscript in this issue of PLoS Genetics sheds lightontohowCdk9functionisintercon- nected with the monoubiquitination of histone H2B in the fission yeast Schizosac- charomycespombe[4]. transcriptional elongation in vitro [16]. Interestingly,thetrimethylationofhistone H3 lysine 4 (H3K4me3) and lysine 79 (H3K79me3) also depend on H2Bub1 [17–19],althoughitsimportancetomam- malian H3K4me3 may be more limited [20,21]. linear pathway. In fact, blocking H2B monoubiquitination by replacing the ubi- quitinatedlysineinH2Bwithanarginine (K119R) leads to decreased recruitment of spCdk9 and reduced levels of Spt5 phosphorylation. Does this mean that spCdk9 and H2Bub1 play opposing roles in fission yeast?Phenotypicstudiessuggestthatthis maybeatleastpartiallytrue.Forexample, whileH2BK119Rmutationordeletionof theS.pombeH2BubiquitinligaseBrl2both lead to septation defects, these can be rescuedbyblockingspCdk9.Furthermore, compound mutants of Spt5 and Set1 suggest that the phenotypic effects of H2Bub1 loss may be due to