|
|
|
|
Research Papers
Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia 19104-6148.
Abstract
Using defined regions of the immunoglobulin heavy-chain enhancer linked to minimal promoters and cDNAs that encode the two helix-loop-helix transcription factors ITF-1 and TFE3, we demonstrate that activity of an otherwise repressed enhancer can be stimulated in nonlymphoid cells. Repression in non-B cells is mediated by the microE5 motif. Derepression occurs at two levels. First, overexpression of ITF-1, and E12/E47-related protein that binds the microE5 motif, leads to transcriptional activation itself. Second, binding of ITF-1 physically displaces a repressor that normally blocks the stimulatory activity of TFE3, which binds the neighboring microE3 motif. TFE3 can only stimulate enhancer activity in the presence of ITF-1 or in the absence of a microE5 motif. Hence, one component of the enhancer's cell type specificity can be artificially modulated through a "genetic switch" in which activity is dictated by the relative levels of ITF-1 and a competing repressor.
This article has been cited by other articles:
![]() |
C. Huan, D. Sashital, T. Hailemariam, M. L. Kelly, and C. A. J. Roman Renal Carcinoma-associated Transcription Factors TFE3 and TFEB Are Leukemia Inhibitory Factor-responsive Transcription Activators of E-cadherin J. Biol. Chem., August 26, 2005; 280(34): 30225 - 30235. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Wang, H. Liu, C. M. Lin, M. I. Aladjem, and E. M. Epner Targeted Deletion of the Chicken {beta}-Globin Regulatory Elements Reveals a Cooperative Gene Silencing Activity J. Biol. Chem., June 17, 2005; 280(24): 23340 - 23348. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Song, J. Cooperman, D. L. Letting, G. A. Blobel, and J. K. Choi Identification of Cyclin D3 as a Direct Target of E2A Using DamID Mol. Cell. Biol., October 1, 2004; 24(19): 8790 - 8802. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.-Y. Kim, K. Chu, H.-J. Kim, H.-A Seong, K.-C. Park, S. Sanyal, J. Takeda, H. Ha, M. Shong, M.-J. Tsai, et al. Orphan Nuclear Receptor Small Heterodimer Partner, a Novel Corepressor for a Basic Helix-Loop-Helix Transcription Factor BETA2/NeuroD Mol. Endocrinol., April 1, 2004; 18(4): 776 - 790. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. I. T. Heng and S.-S. Tan Cloning and Characterization of GRIPE, a Novel Interacting Partner of the Transcription Factor E12 in Developing Mouse Forebrain J. Biol. Chem., November 1, 2002; 277(45): 43152 - 43159. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Zhao, A. Vilardi, R. J. Neely, and J. K. Choi Promotion of Cell Cycle Progression by Basic Helix-Loop-Helix E2A Mol. Cell. Biol., September 15, 2001; 21(18): 6346 - 6357. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. A. Postigo and D. C. Dean Differential expression and function of members of the zfh-1 family of zinc finger/homeodomain repressors PNAS, June 6, 2000; 97(12): 6391 - 6396. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Sigvardsson Overlapping Expression of Early B-Cell Factor and Basic Helix-Loop-Helix Proteins as a Mechanism To Dictate B-Lineage-Specific Activity of the lambda 5 Promoter Mol. Cell. Biol., May 15, 2000; 20(10): 3640 - 3654. [Abstract] [Full Text] |
||||
![]() |
Z. Wang, A. Goldstein, R.-T. Zong, D. Lin, E. J. Neufeld, R. H. Scheuermann, and P. W. Tucker Cux/CDP Homeoprotein Is a Component of NF-µNR and Represses the Immunoglobulin Heavy Chain Intronic Enhancer by Antagonizing the Bright Transcription Activator Mol. Cell. Biol., January 1, 1999; 19(1): 284 - 295. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Dang, X.-h. Sun, and R. Sen ETS-Mediated Cooperation between Basic Helix-Loop-Helix Motifs of the Immunoglobulin µ Heavy-Chain Gene Enhancer Mol. Cell. Biol., March 1, 1998; 18(3): 1477 - 1488. [Abstract] [Full Text] |
||||
![]() |
E. Rao, W. Dang, G. Tian, and R. Sen A Three-protein-DNA Complex on a B Cell-specific Domain of the ImmunoglobulinµHeavy Chain Gene Enhancer J. Biol. Chem., March 7, 1997; 272(10): 6722 - 6732. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Chu, J. Cogswell, and D. S. Kohtz MyoD Functions as a Transcriptional Repressor in Proliferating Myoblasts J. Biol. Chem., February 7, 1997; 272(6): 3145 - 3148. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. L. Roberts, P. Lauzurica, and M. S. Krangel Developmental Regulation of VDJ Recombination By the Core Fragment of the T Cell Receptor alpha Enhancer J. Exp. Med., January 1, 1997; 185(1): 131 - 140. [Abstract] [Full Text] [PDF] |
||||
![]() |
R Eckner, T P Yao, E Oldread, and D M Livingston Interaction and functional collaboration of p300/CBP and bHLH proteins in muscle and B-cell differentiation. Genes & Dev., October 1, 1996; 10(19): 2478 - 2490. [Abstract] [PDF] |
||||
![]() |
L Desbarats, S Gaubatz, and M Eilers Discrimination between different E-box-binding proteins at an endogenous target gene of c-myc. Genes & Dev., February 15, 1996; 10(4): 447 - 460. [Abstract] [PDF] |
||||
![]() |
H Weintraub, T Genetta, and T Kadesch Tissue-specific gene activation by MyoD: determination of specificity by cis-acting repression elements. Genes & Dev., September 15, 1994; 8(18): 2203 - 2211. [Abstract] [PDF] |
||||
![]() |
L Madisen and M Groudine Identification of a locus control region in the immunoglobulin heavy-chain locus that deregulates c-myc expression in plasmacytoma and Burkitt's lymphoma cells. Genes & Dev., September 15, 1994; 8(18): 2212 - 2226. [Abstract] [PDF] |
||||
![]() |
S Gonzalez-Crespo and M Levine Related target enhancers for dorsal and NF-kappa B signaling pathways Science, April 8, 1994; 264(5156): 255 - 258. [Abstract] [PDF] |
||||
![]() |
B Ferreiro, C Kintner, K Zimmerman, D Anderson, and W. Harris XASH genes promote neurogenesis in Xenopus embryos Development, January 12, 1994; 120(12): 3649 - 3655. [Abstract] [PDF] |
||||
![]() |
T Jenuwein, W C Forrester, R G Qiu, and R Grosschedl The immunoglobulin mu enhancer core establishes local factor access in nuclear chromatin independent of transcriptional stimulation. Genes & Dev., October 1, 1993; 7(10): 2016 - 2032. [Abstract] [PDF] |
||||
![]() |
B Nelsen, G Tian, B Erman, J Gregoire, R Maki, B Graves, and R Sen Regulation of lymphoid-specific immunoglobulin mu heavy chain gene enhancer by ETS-domain proteins Science, July 2, 1993; 261(5117): 82 - 86. [Abstract] [PDF] |
||||
![]() |
B. Kreider, R Benezra, G Rovera, and T Kadesch Inhibition of myeloid differentiation by the helix-loop-helix protein Id Science, March 27, 1992; 255(5052): 1700 - 1702. [Abstract] [PDF] |
||||
![]() |
T. Williams, D Moolten, J Burlein, J Romano, R Bhaerman, A Godillot, M Mellon, F. Rauscher 3rd, and J. Kant Identification of a zinc finger protein that inhibits IL-2 gene expression Science, December 20, 1991; 254(5039): 1791 - 1794. [Abstract] [PDF] |
||||
![]() |
M Schlissel, A Voronova, and D Baltimore Helix-loop-helix transcription factor E47 activates germ-line immunoglobulin heavy-chain gene transcription and rearrangement in a pre-T-cell line. Genes & Dev., August 1, 1991; 5(8): 1367 - 1376. [Abstract] [PDF] |
||||
![]() |
C. Chu and D. S. Kohtz Identification of the E2A Gene Products as Regulatory Targets of the G1 Cyclin-dependent Kinases J. Biol. Chem., March 9, 2001; 276(11): 8524 - 8534. [Abstract] [Full Text] [PDF] |
||||