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Nucleic Acids Research, 2002, Vol. 30, No. 11 2270-2279
© 2002 Oxford University Press

Synergistic activation of the rat laminin {gamma}1 chain promoter by the gut-enriched Kruppel-like factor (GKLF/KLF4) and Sp1

Yuji Higaki, Daniel Schullery, Yasunobu Kawata, Maria Shnyreva, Christine Abrass and Karol Bomsztyk*

Department of Medicine, Box 356521, University of Washington, Seattle, WA 98195, USA

Laminin is a multifunctional heterotrimeric protein present in extracellular matrix where it regulates processes that compose tissue architecture including cell differentiation. Laminin {gamma}1 is the most widely expressed laminin chain and its absence causes early lethality in mouse embryos. Laminin {gamma}1 chain gene (LAMC1) promoter contains several GC/GT-rich motifs including the bcn-1 element. Using the bcn-1 element as a bait in the yeast one-hybrid screen, we cloned the gut-enriched Kruppel-like factor (GKLF or KLF4) from a rat mesangial cell library. We show that GKLF binds bcn-1, but this binding is not required for the GKLF-mediated activation of the LAMC1 promoter. The activity of GKLF is dependent on a synergism with another Kruppel-like factor, Sp1. The LAMC1 promoter appears to have multiple GKLF- and Sp1-responsive elements which may account for the synergistic activation. We provide evidence that the synergistic action of GKLF and Sp1 is dependent on the promoter context and the integrity of GKLF activation and DNA-binding domain. GKLF is thought to participate in the switch from cell proliferation to differentiation. Thus, the Sp1–GKLF synergistic activation of the LAMC1 promoter may be one of the avenues for expression of laminin {gamma}1 chain when laminin is needed to regulate cell differentiation.

* To whom correspondence should be addressed. Tel: +1 206 543 3792; Fax: +1 206 685 8661; Email: karolb{at}u.washington.edu


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