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The HDAC-Associated Sin3B Protein Represses DREAM Complex Targets and Cooperates with APC/C to Promote Quiescence

The mammalian DREAM complex is responsible for the transcriptional repression of hundreds of cell-cycle-related genes in quiescence. How the DREAM complex recruits chromatin-modifying entities to aid in its repression remains unknown. Using unbiased proteomics analysis, we have uncovered a robust as...

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Detalles Bibliográficos
Autores principales: Bainor, Anthony J., Saini, Siddharth, Calderon, Alexander, Casado-Polanco, Raquel, Giner-Ramirez, Belén, Moncada, Claudia, Cantor, David J., Ernlund, Amanda, Litovchick, Larisa, David, Gregory
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324198/
https://www.ncbi.nlm.nih.gov/pubmed/30517867
http://dx.doi.org/10.1016/j.celrep.2018.11.024
Descripción
Sumario:The mammalian DREAM complex is responsible for the transcriptional repression of hundreds of cell-cycle-related genes in quiescence. How the DREAM complex recruits chromatin-modifying entities to aid in its repression remains unknown. Using unbiased proteomics analysis, we have uncovered a robust association between the chromatin-associated Sin3B protein and the DREAM complex. We have determined that genetic inactivation of Sin3B results in the de-repression of DREAM target genes during quiescence but is insufficient to allow quiescent cells to resume proliferation. However, inactivation of APC/C(CDH1) was sufficient for Sin3B(−/−) cells, but not parental cells, to re-enter the cell cycle. These studies identify Sin3B as a transcriptional corepressor associated with the DREAM complex in quiescence and reveals a functional cooperation between E2F target repression and APC/C(CDH1) in the negative regulation of cell-cycle progression.