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HDAC activity is dispensable for repression of cell-cycle genes by DREAM and E2F:RB complexes
Nature Communications ( IF 14.7 ) Pub Date : 2024-05-24 , DOI: 10.1038/s41467-024-48724-0
Alison K Barrett 1 , Manisha R Shingare 1 , Andreas Rechtsteiner 2 , Kelsie M Rodriguez 1 , Quynh N Le 1 , Tilini U Wijeratne 1 , Corbin E Mitchell 1 , Miles W Membreno 1 , Seth M Rubin 1 , Gerd A Müller 1
Affiliation  

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.



中文翻译:


HDAC 活性对于 DREAM 和 E2F:RB 复合物抑制细胞周期基因来说是可有可无的



组蛋白脱乙酰酶 (HDAC) 在转录调节中发挥着至关重要的作用,并与包括癌症在内的多种疾病有关。它们参与组蛋白尾部脱乙酰化并与转录抑制典型相关。先前的研究表明,HDAC 通过视网膜母细胞瘤 (RB) 蛋白或通过 SIN3B 的 DREAM 复合物招募到细胞周期基因启动子,对于细胞周期停滞和退出期间的 G1/S 和 G2/M 基因抑制至关重要。在这里,我们研究了 DREAM、RB、SIN3 蛋白和 HDAC 在细胞周期基因抑制背景下的相互作用。 SIN3B 的敲除不会全面抑制非增殖 HCT116 和 C2C12 细胞中的细胞周期基因。 SIN3A/B 的缺失会适度上调 HCT116 细胞中的几个细胞周期基因,但其作用与 DREAM/RB 无关。 HDAC 抑制不会诱导停滞的转化或非转化细胞中 RB/DREAM 靶基因的普遍上调。我们的研究结果表明,E2F:RB 和 DREAM 复合物可以抑制细胞周期基因,而不依赖于 HDAC 活性。

更新日期:2024-05-25
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