RESUMO
Histone deacetylases (HDACs) play a crucial role in transcriptional regulation and are implicated in various diseases, including cancer. They are involved in histone tail deacetylation and canonically linked to transcriptional repression. Previous studies suggested that HDAC recruitment to cell-cycle gene promoters via the retinoblastoma (RB) protein or the DREAM complex through SIN3B is essential for G1/S and G2/M gene repression during cell-cycle arrest and exit. Here we investigate the interplay among DREAM, RB, SIN3 proteins, and HDACs in the context of cell-cycle gene repression. Knockout of SIN3B does not globally derepress cell-cycle genes in non-proliferating HCT116 and C2C12 cells. Loss of SIN3A/B moderately upregulates several cell-cycle genes in HCT116 cells but does so independently of DREAM/RB. HDAC inhibition does not induce general upregulation of RB/DREAM target genes in arrested transformed or non-transformed cells. Our findings suggest that E2F:RB and DREAM complexes can repress cell-cycle genes without relying on HDAC activity.
Assuntos
Fatores de Transcrição E2F , Histona Desacetilases , Proteínas Repressoras , Proteína do Retinoblastoma , Humanos , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Células HCT116 , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Fatores de Transcrição E2F/metabolismo , Fatores de Transcrição E2F/genética , Proteína do Retinoblastoma/metabolismo , Proteína do Retinoblastoma/genética , Camundongos , Animais , Complexo Correpressor Histona Desacetilase e Sin3/metabolismo , Complexo Correpressor Histona Desacetilase e Sin3/genética , Proteínas Interatuantes com Canais de Kv/metabolismo , Proteínas Interatuantes com Canais de Kv/genética , Ciclo Celular/genética , Regiões Promotoras Genéticas/genética , Regulação da Expressão Gênica , Genes cdcRESUMO
Histone deacetylases (HDACs) are pivotal in transcriptional regulation, and their dysregulation has been associated with various diseases including cancer. One of the critical roles of HDAC-containing complexes is the deacetylation of histone tails, which is canonically linked to transcriptional repression. Previous research has indicated that HDACs are recruited to cell-cycle gene promoters through the RB protein or the DREAM complex via SIN3B and that HDAC activity is essential for repressing G1/S and G2/M cell-cycle genes during cell-cycle arrest and exit. In this study, we sought to explore the interdependence of DREAM, RB, SIN3 proteins, and HDACs in the context of cell-cycle gene repression. We found that genetic knockout of SIN3B did not lead to derepression of cell-cycle genes in non-proliferating HCT116 and C2C12 cells. A combined loss of SIN3A and SIN3B resulted in a moderate upregulation in mRNA expression of several cell-cycle genes in arrested HCT116 cells, however, these effects appeared to be independent of DREAM or RB. Furthermore, HDAC inhibition did not induce a general upregulation of RB and DREAM target gene expression in arrested transformed or non-transformed cells. Our findings provide evidence that E2F:RB and DREAM complexes can repress cell-cycle genes without reliance on HDAC activity.