Transcriptional Repression by the Retinoblastoma Protein through the Recruitment of a Histone Methyltransferase

Abstract

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 heterochromatinassociated 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.

Multiple mechanisms of estrogen receptor gene repression contribute to ER-negative breast cancer

“…The methyltransferase SUV39H1 selectively methylates lysine 9 of histone H3, leading to the binding of the heterochromatin protein HP1 and gene silencing in several experimental settings. 9 Here, SUV39H1 is part of the complex shared by both cell lines, but clearly does not repress ERa in MCF-7 cells. Is lysine 9 in histone H3 methylated and HP1 bound in MDA-MB-231 cells?…”

Epigenetic Information and Estrogen Receptor Alpha Expression in Breast Cancer

“…SUV39H1 is also involved in transcriptional repression by the retinoblastoma protein Rb [34,40,41]. SUV39H1 creates a high-affinity binding site for proteins of the HP1 family, and its activity is required for the proper localization of HP1 at heterochromatic sites [34,42,43].…”

DNA-binding independent cell death from a minimal proapoptotic region of E2F-1

“…During quiescence, 'activating' E2F/DP complexes (those containing a DP protein and either E2F-1, -2 or -3) are bound to DNA in a ternary complex with pRb, blocking the ability of E2F to engage the basic transcriptional machinery. Additionally, active repression occurs through the ability of pRb to recruit histone deacetylases and methyltransferases that modify histones and switch off transcription (Magnaghi-Jaulin et al, 1998;Nielsen et al, 2001;Vandel et al, 2001). Following mitogenic stimulation, phosphorylation of pRb by cyclin-dependent kinase (cdk) complexes results in dissociation of pRb from E2F, permitting target gene activation and subsequent cell cycle progression .…”