LMCD1/Dyxin is a novel transcriptional cofactor that restricts GATA6 function by inhibiting DNA binding.

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.
Mesh Terms:
Active Transport, Cell Nucleus, Animals, Base Sequence, Carrier Proteins, DNA, Fetal Heart, Gene Expression Regulation, Developmental, Humans, Lung, Mice, Protein Binding, Protein Structure, Tertiary, RNA, Messenger, RNA, Small Interfering, Recombinant Proteins, Transcription Factors, Two-Hybrid System Techniques
Mol. Cell. Biol.
Date: Oct. 01, 2005
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