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Am J Physiol Gastrointest Liver Physiol 291: G297-G306, 2006. First published April 6, 2006; doi:10.1152/ajpgi.00422.2003
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MUCOSAL BIOLOGY

Cooperative interactions among intestinal GATA factors in activating the rat liver fatty acid binding protein gene

Joyce K. Divine,1,2 Lora J. Staloch,2 Hanna Haveri,3 Christopher W. Rowley,2 Markku Heikinheimo,3 and Theodore C. Simon2

1Division of Biology and Biomedical Sciences and 2Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri; and 3Children’s Hospital and Program for Developmental and Reproductive Biology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland

Submitted 25 September 2003 ; accepted in final form 21 February 2006

GATA-4, GATA-5, and GATA-6 are endodermal zinc-finger transcription factors that activate numerous enterocytic genes. GATA-4 and GATA-6 but not GATA-5 are present in adult murine small intestinal enterocytes, and we now report the simultaneous presence of all three GATA factors in murine small intestinal enterocytes before weaning age. An immunohistochemical survey detected enterocytic GATA-4 and GATA-6 at birth and 1 wk of age and GATA-5 at 1 wk but not birth. Interactions among GATA factors were explored utilizing a transgene constructed from the proximal promoter of the rat liver fatty acid binding protein gene (Fabp1). GATA-4 and GATA-5 but not GATA-6 activate the Fabp1 transgene through a cognate binding site at –128. A dose-response assay revealed a maximum in transgene activation by both factors, where additional factor did not further increase transgene activity. However, at saturated levels of GATA-4, additional transgene activation was achieved by adding GATA-5 expression construct, and vice versa. Similar cooperativity occurred with GATA-5 and GATA-6. Identical interactions were observed with a target transgene consisting of a single GATA site upstream of a minimal promoter. Furthermore, GATA-4 and GATA-5 or GATA-5 and GATA-6 bound to each other in solution. These results are consistent with tethering of one GATA factor to the Fabp1 promoter through interaction with a second GATA factor to produce increased target gene activation. Cooperative target gene activation was specific to an intestinal cell line and may represent a mechanism by which genes are activated in the small intestinal epithelium during the period before weaning.

fabp1; GATA-4; GATA-5; GATA-6; suckling-weaning transition



Address for reprint requests and other correspondence: T. C. Simon, Washington Univ. School of Medicine, Dept. of Pediatrics, Campus Box 8208, St. Louis, MO 63110 (e-mail: simon_t{at}kids.wustl.edu)




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