| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
activates liver fatty acid binding protein gene cooperatively with endodermal transcription factors: MODY3 mutations selectively abrogate cooperativity
1 Department of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, USA; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
2 Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
* To whom correspondence should be addressed. E-mail: simon_t{at}kids.wustl.edu.
HNF-1
plays a central role in intestinal and hepatic gene regulation, and is required for hepatic expression of the liver fatty acid binding protein gene (Fabpl). An Fabpl transgene is directly activated through cognate sites by HNF-1 and HNF-1
, as well as five other endodermal factors: CDX-1, C/EBP, GATA-4, FoxA2, and HNF-4. HNF-1 activated the Fabpl transgene up to sixty-fold greater in the presence the other five endodermal factors than in their absence, accounting for up to half the total transgene activation by the group of six factors. This degree of synergistic interaction suggests that multi-factor cooperativity is a critical determinant of endodermal gene activation by HNF-1. Mutations in HNF-1 that result in maturity onset diabetes of the young (MODY3) provide evidence for the in vivo significance of these synergistic interactions. An R131Q HNF-1 MODY3 mutant exhibits complete loss of synergistic activation in concert with the other endodermal transcription factors despite wild type transactivation ability in their absence. Furthermore, while wild-type HNF-1 exhibited pairwise cooperative synergy with each of the other five factors, the R131Q mutant could synergize only with GATA-4 and C/EBP. Selective loss of synergy with other endodermal transcription factors accompanied by retention of native transactivation ability in an HNF-1 MODY mutant suggests the in vivo significance of cooperative synergy.
This article has been cited by other articles:
|
|
 |
|
  M. Yu, J. Wang, W. Li, Y. Z. Yuan, C. Y. Li, X. H. Qian, W. X. Xu, Y. Q. Zhan, and X. M. Yang Proteomic screen defines the hepatocyte nuclear factor 1{alpha}-binding partners and identifies HMGB1 as a new cofactor of HNF1{alpha} Nucleic Acids Res., March 27, 2008; 36(4): 1209 - 1219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Jeong, H.-S. Lee, K.-S. Kim, Y.-K. Kim, D. Yoon, and S. W. Park Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2 J. Lipid Res., February 1, 2008; 49(2): 399 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. S. Belaguli, M. Zhang, M. Rigi, M. Aftab, and D. H. Berger Cooperation between GATA4 and TGF-beta signaling regulates intestinal epithelial gene expression Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1520 - G1533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Bosse, J. J. Fialkovich, C. M. Piaseckyj, E. Beuling, H. Broekman, R. J. Grand, R. K. Montgomery, and S. D. Krasinski Gata4 and Hnf1{alpha} are partially required for the expression of specific intestinal genes during development Am J Physiol Gastrointest Liver Physiol, May 1, 2007; 292(5): G1302 - G1314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Divine, L. J. Staloch, H. Haveri, C. W. Rowley, M. Heikinheimo, and T. C. Simon Cooperative interactions among intestinal GATA factors in activating the rat liver fatty acid binding protein gene Am J Physiol Gastrointest Liver Physiol, August 1, 2006; 291(2): G297 - G306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Bosse, H. M. van Wering, M. Gielen, L. N. Dowling, J. J. Fialkovich, C. M. Piaseckyj, F. J. Gonzalez, T. E. Akiyama, R. K. Montgomery, R. J. Grand, et al. Hepatocyte nuclear factor-1{alpha} is required for expression but dispensable for histone acetylation of the lactase-phlorizin hydrolase gene in vivo Am J Physiol Gastrointest Liver Physiol, May 1, 2006; 290(5): G1016 - G1024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. W. Rowley, L. J. Staloch, J. K. Divine, S. P. McCaul, and T. C. Simon Mechanisms of mutual functional interactions between HNF-4{alpha} and HNF-1{alpha} revealed by mutations that cause maturity onset diabetes of the young Am J Physiol Gastrointest Liver Physiol, March 1, 2006; 290(3): G466 - G475. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Divine, L. J. Staloch, H. Haveri, C. M. Jacobsen, D. B. Wilson, M. Heikinheimo, and T. C. Simon GATA-4, GATA-5, and GATA-6 activate the rat liver fatty acid binding protein gene in concert with HNF-1{alpha} Am J Physiol Gastrointest Liver Physiol, November 1, 2004; 287(5): G1086 - G1099. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. van Wering, T. Bosse, A. Musters, E. de Jong, N. de Jong, C. E. Hogen Esch, F. Boudreau, G. P. Swain, L. N. Dowling, R. K. Montgomery, et al. Complex regulation of the lactase-phlorizin hydrolase promoter by GATA-4 Am J Physiol Gastrointest Liver Physiol, October 1, 2004; 287(4): G899 - G909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Oesterreicher and S. J. Henning Rapid induction of GATA transcription factors in developing mouse intestine following glucocorticoid administration Am J Physiol Gastrointest Liver Physiol, June 1, 2004; 286(6): G947 - G953. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
