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Molecular and Cellular Biology, October 2005, p. 8864-8873, Vol. 25, No. 20
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.20.8864-8873.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

LMCD1/Dyxin Is a Novel Transcriptional Cofactor That Restricts GATA6 Function by Inhibiting DNA Binding

Nibedita Rath,1 Zhishan Wang,1 Min Min Lu,1 and Edward E. Morrisey1,2*

Department of Medicine and Molecular Cardiology Research Center,1 Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania 191042

Received 19 November 2004/ Returned for modification 30 December 2004/ Accepted 16 July 2005

The activity of GATA factors is regulated, in part, at the level of protein-protein interactions. LIM domain proteins, first defined by the zinc finger motifs found in the Lin11, Isl-1, and Mec-3 proteins, act as coactivators of GATA function in both hematopoietic and cardiovascular tissues. We have identified a novel GATA-LIM interaction between GATA6 and LMCD1/dyxin. The LIM domains and cysteine-rich domains in LMCD1/dyxin and the carboxy-terminal zinc finger of GATA6 mediate this interaction. Expression of LMCD1/dyxin is remarkably similar to that of GATA6, with high-level expression observed in distal airway epithelium of the lung, vascular smooth muscle, and myocardium. In contrast to other GATA-LIM protein interactions, LMCD1/dyxin represses GATA6 activation of both lung and cardiac tissue-specific promoters. Electrophoretic mobility shift and chromatin immunoprecipitation assays show that LMCD1/dyxin represses GATA6 function by inhibiting GATA6 DNA binding. These data reveal an interaction between GATA6 and LMCD1/dyxin and demonstrate a novel mechanism through which LIM proteins can assert their role as transcriptional cofactors of GATA proteins.

* Corresponding author. Mailing address: University of Pennsylvania, 956 BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104. Phone: (215) 573-3010. Fax: (215) 573-2094. E-mail: emorrise{at}mail.med.upenn.edu.

Molecular and Cellular Biology, October 2005, p. 8864-8873, Vol. 25, No. 20
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.20.8864-8873.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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