The human synMuv-like protein LIN-9 is required for transcription of G2/M genes and for entry into mitosis.
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.
Osterloh
Lisa
L
Department of Physiological Chemistry I, Biocenter, University of Würzburg, Am Hubland, Würzburg, Germany.
von Eyss
Björn
B
Schmit
Fabienne
F
Rein
Lena
L
Hübner
Denise
D
Samans
Birgit
B
Hauser
Stefanie
S
Gaubatz
Stefan
S
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*
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