Pile Lori A, Schlag Erin M, Wassarman David A
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Mol Cell Biol. 2002 Jul;22(14):4965-76. doi: 10.1128/MCB.22.14.4965-4976.2002.
The SIN3 corepressor and RPD3 histone deacetylase are components of the evolutionarily conserved SIN3/RPD3 transcriptional repression complex. Here we show that the SIN3/RPD3 complex and the corepressor SMRTER are required for Drosophila G(2) phase cell cycle progression. Loss of the SIN3, but not the p55, SAP18, or SAP30, component of the SIN3/RPD3 complex by RNA interference (RNAi) causes a cell cycle delay prior to initiation of mitosis. Loss of RPD3 reduces the growth rate of cells but does not cause a distinct cell cycle defect, suggesting that cells are delayed in multiple phases of the cell cycle, including G(2). Thus, the role of the SIN3/RPD3 complex in G(2) phase progression appears to be independent of p55, SAP18, and SAP30. SMRTER protein levels are reduced in SIN3 and RPD3 RNAi cells, and loss of SMRTER by RNAi is sufficient to cause a G(2) phase delay, demonstrating that regulation of SMRTER protein levels by the SIN3/RPD3 complex is a vital component of the transcriptional repression mechanism. Loss of SIN3 does not affect global acetylation of histones H3 and H4, suggesting that the G(2) phase delay is due not to global changes in genome integrity but rather to derepression of SIN3 target genes.
SIN3共抑制因子和RPD3组蛋白去乙酰化酶是进化保守的SIN3/RPD3转录抑制复合物的组成部分。我们在此表明，SIN3/RPD3复合物和共抑制因子SMRTER是果蝇G2期细胞周期进程所必需的。通过RNA干扰（RNAi）使SIN3/RPD3复合物中的SIN3而非p55、SAP18或SAP30成分缺失，会导致有丝分裂开始前的细胞周期延迟。RPD3的缺失会降低细胞的生长速率，但不会导致明显的细胞周期缺陷，这表明细胞在细胞周期的多个阶段包括G2期被延迟。因此，SIN3/RPD3复合物在G2期进程中的作用似乎独立于p55、SAP18和SAP30。在SIN3和RPD3 RNAi细胞中，SMRTER蛋白水平降低，并且通过RNAi使SMRTER缺失足以导致G2期延迟，这表明SIN3/RPD3复合物对SMRTER蛋白水平的调节是转录抑制机制的一个重要组成部分。SIN3的缺失不会影响组蛋白H3和H4的整体乙酰化，这表明G2期延迟不是由于基因组完整性的整体变化，而是由于SIN3靶基因的去抑制。
