This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Duan, Z. Articles by Horwitz, M. Search for Related Content PubMed PubMed Citation Articles by Duan, Z. Articles by Horwitz, M.

Gfi1 Coordinates Epigenetic Repression of p21^Cip/WAF1 by Recruitment of Histone Lysine Methyltransferase G9a and Histone Deacetylase 1

Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Box 357720, Seattle, Washington 98195,¹ Institute for Cellular Therapeutics and Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky 40202²

Received 27 May 2005/ Returned for modification 23 June 2005/ Accepted 14 September 2005

The growth factor independent 1 (Gfi1) transcriptional regulator oncoprotein plays a crucial role in hematopoietic, inner ear, and pulmonary neuroendocrine cell development and governs cell processes as diverse as self-renewal of hematopoietic stem cells, proliferation, apoptosis, differentiation, cell fate specification, and oncogenesis. However, the molecular basis of its transcriptional functions has remained elusive. Here we show that Gfi1 recruits the histone lysine methyltransferase G9a and the histone deacetylase 1 (HDAC1) in order to modify the chromatin of genes targeted for repression by Gfi1. G9a and HDAC1 are both in a repressive complex assembled by Gfi1. Endogenous Gfi1 colocalizes with G9a, HDAC1, and K9-dimethylated histone H3. Gfi1 associates with G9a and HDAC1 on the promoter of the cell cycle regulator p21^Cip/WAF1, resulting in an increase in K9 dimethylation at histone H3. Silencing of Gfi1 expression in myeloid cells reverses G9a and HDAC1 recruitment to p21^Cip/WAF1 and elevates its expression. These findings highlight the role of epigenetics in the regulation of development and oncogenesis by Gfi1.

This article has been cited by other articles:

• Jepsen, K., Gleiberman, A. S., Shi, C., Simon, D. I., Rosenfeld, M. G. (2008). Cooperative regulation in development by SMRT and FOXP1. Genes Dev. 22: 740-745 [Abstract] [Full Text]  
• Wagschal, A., Sutherland, H. G., Woodfine, K., Henckel, A., Chebli, K., Schulz, R., Oakey, R. J., Bickmore, W. A., Feil, R. (2008). G9a Histone Methyltransferase Contributes to Imprinting in the Mouse Placenta. Mol. Cell. Biol. 28: 1104-1113 [Abstract] [Full Text]  
• Abukhdeir, A. M., Vitolo, M. I., Argani, P., De Marzo, A. M., Karakas, B., Konishi, H., Gustin, J. P., Lauring, J., Garay, J. P., Pendleton, C., Konishi, Y., Blair, B. G., Brenner, K., Garrett-Mayer, E., Carraway, H., Bachman, K. E., Park, B. H. (2008). Tamoxifen-stimulated growth of breast cancer due to p21 loss. Proc. Natl. Acad. Sci. USA 105: 288-293 [Abstract] [Full Text]  
• Duan, Z., Person, R. E., Lee, H.-H., Huang, S., Donadieu, J., Badolato, R., Grimes, H. L., Papayannopoulou, T., Horwitz, M. S. (2007). Epigenetic Regulation of Protein-Coding and MicroRNA Genes by the Gfi1-Interacting Tumor Suppressor PRDM5. Mol. Cell. Biol. 27: 6889-6902 [Abstract] [Full Text]  
• Moroy, T., Heyd, F. (2007). The impact of alternative splicing in vivo: Mouse models show the way. RNA 13: 1155-1171 [Abstract] [Full Text]  
• Smallwood, A., Esteve, P.-O., Pradhan, S., Carey, M. (2007). Functional cooperation between HP1 and DNMT1 mediates gene silencing. Genes Dev. 21: 1169-1178 [Abstract] [Full Text]  
• Vassen, L., Okayama, T., Moroy, T. (2007). Gfi1b:green fluorescent protein knock-in mice reveal a dynamic expression pattern of Gfi1b during hematopoiesis that is largely complementary to Gfi1. Blood 109: 2356-2364 [Abstract] [Full Text]  
• Zhao, L. Y., Santiago, A., Liu, J., Liao, D. (2007). Repression of p53-mediated Transcription by Adenovirus E1B 55-kDa Does Not Require Corepressor mSin3A and Histone Deacetylases. J. Biol. Chem. 282: 7001-7010 [Abstract] [Full Text]  
• Fang, S., Miao, J., Xiang, L., Ponugoti, B., Treuter, E., Kemper, J. K. (2007). Coordinated Recruitment of Histone Methyltransferase G9a and Other Chromatin-Modifying Enzymes in SHP-Mediated Regulation of Hepatic Bile Acid Metabolism. Mol. Cell. Biol. 27: 1407-1424 [Abstract] [Full Text]  
• Ueda, J., Tachibana, M., Ikura, T., Shinkai, Y. (2006). Zinc Finger Protein Wiz Links G9a/GLP Histone Methyltransferases to the Co-repressor Molecule CtBP. J. Biol. Chem. 281: 20120-20128 [Abstract] [Full Text]