Cell Growth & Differentiation, Vol 5, Issue 5 467-474, Copyright © 1994 by American Association of Cancer Research

ARTICLES

Characterization of the human RB1 promoter and of elements involved in transcriptional regulation

RM Gill, PA Hamel, J Zhe, E Zacksenhaus, BL Gallie and RA Phillips
Division of Immunology and Cancer Research, Hospital for Sick Children, Toronto, Ontario, Canada.

The retinoblastoma gene (RB1) is a recessive oncogene implicated in a number of human tumors. Although the RB1 gene is expressed in most proliferating cells, there is considerable evidence for the transcriptional regulation of this gene. Therefore, we have performed a detailed analysis of the regulatory elements in the promoter of the human RB1 gene. Deletion analysis of the 5' upstream region determined the location of the basal promoter to be between -208 and -179 nucleotides relative to the translational start. This region contains essential binding sites for the transcription elements ATF and SP1 and potentially important sites for E2F and steroid hormone responsiveness but no TATA or CAAT boxes. Primer extension and RNase protection analysis identified two initiation sites at -176 and -128 base pairs, both downstream of the promoter. Cotransfection experiments revealed repression of the RB1 promoter by its protein product p110RB1. This repression has been mapped to the core promoter region containing the E2F-binding site; however, this site is not required for autorepression.

This article has been cited by other articles:

				M. Agromayor, E. Wloga, B. Naglieri, J. Abrashkin, K. Verma, and L. Yamasaki Visualizing Dynamic E2F-Mediated Repression In Vivo Mol. Cell. Biol., June 15, 2006; 26(12): 4448 - 4461. [Abstract] [Full Text] [PDF]

				B. St-Pierre, X. Liu, L.-C. T. Kha, X. Zhu, O. Ryan, Z. Jiang, and E. Zacksenhaus Conserved and specific functions of mammalian ssu72 Nucleic Acids Res., January 19, 2005; 33(2): 464 - 477. [Abstract] [Full Text] [PDF]

				E. Burnett and P. Tattersall Reverse Genetic System for the Analysis of Parvovirus Telomeres Reveals Interactions between Transcription Factor Binding Sites in the Hairpin Stem J. Virol., August 15, 2003; 77(16): 8650 - 8660. [Abstract] [Full Text] [PDF]

				A. Magenta, C. Cenciarelli, F. De Santa, P. Fuschi, F. Martelli, M. Caruso, and A. Felsani MyoD Stimulates RB Promoter Activity via the CREB/p300 Nuclear Transduction Pathway Mol. Cell. Biol., April 15, 2003; 23(8): 2893 - 2906. [Abstract] [Full Text] [PDF]

				J. Botos, R. Smith III, and D. T. Kochevar Retinoblastoma Function Is a Better Indicator of Cellular Phenotype in Cultured Breast Adenocarcinoma Cells than Retinoblastoma Expression Experimental Biology and Medicine, May 1, 2002; 227(5): 354 - 362. [Abstract] [Full Text] [PDF]

				V. D. Brown and B. L. Gallie The B-Domain Lysine Patch of pRB Is Required for Binding to Large T Antigen and Release of E2F by Phosphorylation Mol. Cell. Biol., March 1, 2002; 22(5): 1390 - 1401. [Abstract] [Full Text] [PDF]

				R. M. Gill and P. A. Hamel Subcellular Compartmentalization of E2F Family Members Is Required for Maintenance of the Postmitotic State in Terminally Differentiated Muscle J. Cell Biol., March 20, 2000; 148(6): 1187 - 1202. [Abstract] [Full Text] [PDF]

				D. J. Simpson, N. A. Hibberts, A. M. McNicol, R. N. Clayton, and W. E. Farrell Loss of pRb Expression in Pituitary Adenomas Is Associated with Methylation of the RB1 CpG Island Cancer Res., March 1, 2000; 60(5): 1211 - 1216. [Abstract] [Full Text]

				K. Nolan, J. Lacoste, and J. T. Parsons Regulated Expression of Focal Adhesion Kinase-Related Nonkinase, the Autonomously Expressed C-Terminal Domain of Focal Adhesion Kinase Mol. Cell. Biol., September 1, 1999; 19(9): 6120 - 6129. [Abstract] [Full Text] [PDF]

				A. Tamir, J. Howard, R. R. Higgins, Y.-J. Li, L. Berger, E. Zacksenhaus, M. Reis, and Y. Ben-David Fli-1, an Ets-Related Transcription Factor, Regulates Erythropoietin-Induced Erythroid Proliferation and Differentiation: Evidence for Direct Transcriptional Repression of the Rb Gene during Differentiation Mol. Cell. Biol., June 1, 1999; 19(6): 4452 - 4464. [Abstract] [Full Text] [PDF]

				E. S. Knudsen, C. Buckmaster, T.-T. Chen, J. R. Feramisco, and J. Y.J. Wang Inhibition of DNA synthesis by RB: effects on G1/S transition and S-phase progression Genes & Dev., August 1, 1998; 12(15): 2278 - 2292. [Abstract] [Full Text]

				R K Hurford, D Cobrinik, M H Lee, and N Dyson pRB and p107/p130 are required for the regulated expression of different sets of E2F responsive genes. Genes & Dev., June 1, 1997; 11(11): 1447 - 1463. [Abstract] [PDF]

				Z. Jiang, Z. Guo, F. A. Saad, J. Ellis, and E. Zacksenhaus Retinoblastoma Gene Promoter Directs Transgene Expression Exclusively to the Nervous System J. Biol. Chem., January 5, 2001; 276(1): 593 - 600. [Abstract] [Full Text] [PDF]