LINC, a human complex that is related to pRB-containing complexes in invertebrates regulates the expression of G2/M genes.
Here we report the identification of the LIN complex (LINC), a human multiprotein complex that is required for transcriptional activation of G2/M genes. LINC is related to the recently identified dREAM and DRM complexes of Drosophila and C. elegans that contain homologs of the mammalian retinoblastoma tumor suppressor protein. The LINC core complex consists of at least five subunits including the chromatin-associated LIN-9 and RbAp48 proteins. LINC dynamically associates with pocket proteins, E2F and B-MYB during the cell cycle. In quiescent cells, LINC binds to p130 and E2F4. During cell cycle entry, E2F4 and p130 dissociate and LINC switches to B-MYB and p107. Chromatin Immunoprecipitation experiments demonstrate that LINC associates with a large number of E2F-regulated promoters in quiescent cells. However, RNAi experiments reveal that LINC is not required for repression. In S-phase, LINC selectively binds to the promoters of G2/M genes whose products are required for mitosis and plays an important role in their cell cycle dependent activation.
Department of Physiological Chemistry I, Biocenter, University of Würzburg, Würzburg, Germany.
Fabienne
F
Schmit
Michael
M
Korenjak
Mirijam
M
Mannefeld
Kathrin
K
Schmitt
Claudia
C
Franke
Björn
B
von Eyss
Sladjana
S
Gagrica
Frank
F
Hänel
Alexander
A
Brehm
Stefan
S
Gaubatz
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D050684:E2F Transcription Factors / Q000235:genetics / Q000378:metabolism; D016195:G2 Phase / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D008938:Mitosis / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D050684:E2F Transcription Factors; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D021122:Protein Subunits; D016160:Retinoblastoma Protein; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; C501563:LIN9 protein, human; C523007:LIN37 protein, human; C523006:LIN54 protein, human