title: The MuvB complex sequentially recruits B-Myb and FoxM1 to promote mitotic gene expression.
abstract: Cell cycle progression is dependent on two major waves of gene expression. Early cell cycle gene expression occurs during G1/S to generate factors required for DNA replication, while late cell cycle gene expression begins during G2 to prepare for mitosis. Here we demonstrate that the MuvB complex-comprised of LIN9, LIN37, LIN52, LIN54, and RBBP4-serves an essential role in three distinct transcription complexes to regulate cell cycle gene expression. The MuvB complex, together with the Rb-like protein p130, E2F4, and DP1, forms the DREAM complex during quiescence and represses expression of both early and late genes. Upon cell cycle entry, the MuvB complex dissociates from p130/DREAM, binds to B-Myb, and reassociates with the promoters of late genes during S phase. MuvB and B-Myb are required for the subsequent recruitment of FoxM1 to late gene promoters during G2. The MuvB complex remains bound to FoxM1 during peak late cell cycle gene expression, while B-Myb binding is lost when it undergoes phosphorylation-dependent, proteasome-mediated degradation during late S phase. Our results reveal a novel role for the MuvB complex in recruiting B-Myb and FoxM1 to promote late cell cycle gene expression and in regulating cell cycle gene expression from quiescence through mitosis.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
authors.forename: Subhashini
authors.initials: S
authors.lastname: Sadasivam
authors.forename: Shenghua
authors.initials: S
authors.lastname: Duan
authors.forename: James A
authors.initials: JA
authors.lastname: DeCaprio
mesh_terms: D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D006367:HeLa Cells; D006801:Humans; D051605:Kv Channel-Interacting Proteins / Q000378:metabolism; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D020626:Oncogene Proteins v-myb / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C496749:KCNIP3 protein, human; D051605:Kv Channel-Interacting Proteins; D020626:Oncogene Proteins v-myb; D012097:Repressor Proteins