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| Rb targets histone H3 methylation and HP1 to promoters |
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| Author(s): Nielsen SJ, Schneider R, Bauer UM, Bannister AJ, Morrison A, O'Carroll D, Firestein R, Cleary M, Jenuwein T, Herrera RE, Kouzarides T |
| Source: NATURE Volume: 412 Issue: 6846 Pages: 561-565 Published: AUG 2 2001 |
| Times Cited: 460 References: 19 |
| Abstract: In eukaryotic cells the histone methylase SUV39H1 and the methyl-lysine binding protein HP1 functionally interact to repress transcription at heterochromatic sites(1). Lysine 9 of histone H3 is methylated by SUV39H1 (ref. 2), creating a binding site for the chromo domain of HP1 (refs 3, 4). Here we show that SUV39H1 and HP1 are both involved in the repressive functions of the retinoblastoma (Rb) protein. Rb associates with SUV39H1 and HP1 in vivo by means of its pocket domain. SUV39H1 cooperates with Rb to repress the cyclin E promoter, and in fibroblasts that are disrupted for SUV39, the activity of the cyclin E and cyclin A2 genes are specifically elevated. Chromatin immunoprecipitations show that Rb is necessary to direct methylation of histone H3, and is necessary for binding of HP1 to the cyclin E promoter. These results indicate that the SUV39H1-HP1 complex is not only involved in heterochromatic silencing but also has a role in repression of euchromatic genes by Rb and perhaps other co-repressor proteins. |
| Document Type: Article |
| Language: English |
| Reprint Address: Kouzarides, T (reprint author), Wellcome CRC Inst, Tennis Court Rd, Cambridge CB2 1QR, England |
Addresses:
1. Wellcome CRC Inst, Cambridge CB2 1QR, England
2. Dept Pathol, Cambridge CB2 1QR, England
3. Baylor Coll Med, Dept Mol & Cellular Biol, Breast Ctr, Houston, TX 77030 USA
4. Vienna Bioctr, Res Inst Mol Pathol, A-1030 Vienna, Austria
5. Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA |
| Publisher: MACMILLAN PUBLISHERS LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 458PC |
| ISSN: 0028-0836 |
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