Genetics
Abstract
Research Article
Authors
Oliver G. Opitz, Hideki Harada, Yasir Suliman, Ben Rhoades, Norman E. Sharpless, Ralph Kent, Levy Kopelovich, Hiroshi Nakagawa, Anil K. Rustgi
Abstract
Research Article
Authors
Joëlle Dupont, Jean Pierre Renou, Moshe Shani, Lothar Hennighausen, Derek LeRoith
Abstract
Mutations in the genes encoding hepatocyte nuclear factor 4α (HNF-4α) and HNF-1α impair insulin secretion and cause maturity onset diabetes of the young (MODY). HNF-4α is known to be an essential positive regulator of HNF-1α. More recent data demonstrates that HNF-4α expression is dependent on HNF-1α in mouse pancreatic islets and exocrine cells. This effect is mediated by binding of HNF-1α to a tissue-specific promoter (P2) located 45.6 kb upstream from the previously characterized Hnf4α promoter (P1). Here we report that the expression of HNF-4α in human islets and exocrine cells is primarily mediated by the P2 promoter. Furthermore, we describe a G → A mutation in a conserved nucleotide position of the HNF-1α binding site of the P2 promoter, which cosegregates with MODY. The mutation results in decreased affinity for HNF-1α, and consequently in reduced HNF-1α–dependent activation. These findings provide genetic evidence that HNF-1α serves as an upstream regulator of HNF-4α and interacts directly with the P2 promoter in human pancreatic cells. Furthermore, they indicate that this regulation is essential to maintain normal pancreatic function.
Authors
Sara K. Hansen, Marcelina Párrizas, Maria L. Jensen, Stepanka Pruhova, Jakob Ek, Sylvia F. Boj, Anders Johansen, Miguel A. Maestro, Francisca Rivera, Hans Eiberg, Michal Andel, Jan Lebl, Oluf Pedersen, Jorge Ferrer, Torben Hansen
Abstract
Research Article
Authors
Xinli Zhang, Shun’ichi Kuroda, Dale Carpenter, Ichiro Nishimura, Chia Soo, Rex Moats, Keisuke Iida, Eric Wisner, Fei-Ya Hu, Steve Miao, Steve Beanes, Catherine Dang, Heleni Vastardis, Michael Longaker, Katsuyuki Tanizawa, Norihiro Kanayama, Naoaki Saito, Kang Ting
Abstract
Research Article
Authors
Jennifer M. McCoy, Joan R. Wicks, Laurent P. Audoly
Abstract
Research Article
Authors
Min Li-Weber, Markus A. Weigand, Marco Giaisi, Dorothee Süss, Monika K. Treiber, Sven Baumann, Elena Ritsou, Raoul Breitkreutz, Peter H. Krammer
Abstract
Research Article
Authors
Alberto Auricchio, Erin O’Connor, Daniel Weiner, Guang-Ping Gao, Markus Hildinger, Lili Wang, Roberto Calcedo, James M. Wilson
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Research Article
Authors
Robert Dinser, Frank Zaucke, Florian Kreppel, Kjell Hultenby, Stefan Kochanek, Mats Paulsson, Patrik Maurer
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Research Article
Authors
Kunlin Jin, Xiao Ou Mao, Yunjuan Sun, Lin Xie, David A. Greenberg
Abstract
Research Article
Authors
Joost P. Schanstra, Eric Neau, Pascale Drogoz, Miguel A. Arevalo Gomez, José Miguel Lopez Novoa, Denis Calise, Christiane Pecher, Michael Bader, Jean-Pierre Girolami, Jean-Loup Bascands
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ISSN: 0021-9738 (print), 1558-8238 (online)