title: The human synMuv-like protein LIN-9 is required for transcription of G2/M genes and for entry into mitosis.
abstract: Regulated gene expression is critical for the proper timing of cell cycle transitions. Here we report that human LIN-9 has an important function in transcriptional regulation of G2/M genes. Depletion of LIN-9 by RNAi in human fibroblasts strongly impairs proliferation and delays progression from G2 to M. We identify a cluster of G2/M genes as direct targets of LIN-9. Activation of these genes is linked to an association between LIN-9 and B-MYB. Chromatin immunoprecipitation assays revealed binding of both LIN-9 and B-MYB to the promoters of G2/M regulated genes. Depletion of B-MYB recapitulated the biological outcome of LIN-9 knockdown, including impaired proliferation and reduced expression of G2/M genes. These data suggest a critical role for human LIN-9, together with B-MYB, in the activation of genes that are essential for progression into mitosis.
authors.affiliation: Department of Physiological Chemistry I, Biocenter, University of Würzburg, Am Hubland, Würzburg, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Osterloh
authors.forename: Björn
authors.initials: B
authors.lastname: von Eyss
authors.forename: Fabienne
authors.initials: F
authors.lastname: Schmit
authors.forename: Lena
authors.initials: L
authors.lastname: Rein
authors.forename: Denise
authors.initials: D
authors.lastname: Hübner
authors.forename: Birgit
authors.initials: B
authors.lastname: Samans
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hauser
authors.forename: Stefan
authors.initials: S
authors.lastname: Gaubatz
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D002455:Cell Division; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D016195:G2 Phase; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D005810:Multigene Family; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C501563:LIN9 protein, human; C064352:MYBL2 protein, human; D009687:Nuclear Proteins; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins