Vandel L, Nicolas E, Vaute O, Ferreira R, Ait-Si-Ali S, Trouche D
Laboratoire de Biologie Moléculaire Eucaryote, UMR 5099 CNRS, and Ligue Nationale Contre le Cancer, 31062 Toulouse, France.
Mol Cell Biol. 2001 Oct;21(19):6484-94. doi: 10.1128/MCB.21.19.6484-6494.2001.
The E2F transcription factor controls the cell cycle-dependent expression of many S-phase-specific genes. Transcriptional repression of these genes in G(0) and at the beginning of G(1) by the retinoblasma protein Rb is crucial for the proper control of cell proliferation. Rb has been proposed to function, at least in part, through the recruitment of histone deacetylases. However, recent results indicate that other chromatin-modifying enzymes are likely to be involved. Here, we show that Rb also interacts with a histone methyltransferase, which specifically methylates K9 of histone H3. The results of coimmunoprecipitation experiments of endogenous or transfected proteins indicate that this histone methyltransferase is the recently described heterochromatin-associated protein Suv39H1. Interestingly, phosphorylation of Rb in vitro as well as in vivo abolished the Rb-Suv39H1 interaction. We also found that Suv39H1 and Rb cooperate to repress E2F activity and that Suv39H1 could be recruited to E2F1 through its interaction with Rb. Taken together, these data indicate that Suv39H1 is involved in transcriptional repression by Rb and suggest an unexpected link between E2F regulation and heterochromatin.
E2F转录因子控制许多S期特异性基因的细胞周期依赖性表达。在G(0)期和G(1)期开始时，视网膜母细胞瘤蛋白Rb对这些基因的转录抑制对于细胞增殖的适当控制至关重要。有人提出Rb至少部分地通过募集组蛋白脱乙酰酶发挥作用。然而，最近的结果表明其他染色质修饰酶可能也参与其中。在这里，我们表明Rb还与一种组蛋白甲基转移酶相互作用，该酶特异性地使组蛋白H3的K9甲基化。内源性或转染蛋白的共免疫沉淀实验结果表明，这种组蛋白甲基转移酶是最近描述的异染色质相关蛋白Suv39H1。有趣的是，Rb在体外和体内的磷酸化都消除了Rb与Suv39H1的相互作用。我们还发现Suv39H1和Rb协同抑制E2F活性，并且Suv39H1可以通过与Rb的相互作用被募集到E2F1。综上所述，这些数据表明Suv39H1参与了Rb介导的转录抑制，并提示了E2F调节与异染色质之间意想不到的联系。
