Functional analysis and chromosomal mapping of Gata5, a gene encoding a zinc finger DNA-binding protein

The GATA family of zinc finger proteins are transcriptional regulators with critical functions in lineage differentiation and embryonic development. B ased on structural and expression pattern comparisons, the GATA proteins ha ve been subdivided into two groups. The first subgroup consists of GATA-1, -2, and 3, which are all highly expressed in the hematopoietic system, wher eas GATA-4, -5, and -6 are present essentially in the heart and gut. We hav e isolated and functionally characterized the rat GATA-5 cDNA, which encode s a 45-kDa protein with 71%, 73%, and 97% homology to its amphibian, avian, and murine homologs, respectively. Northern blot analysis showed that rat GATA-5 is expressed in a dynamic pattern during embryonic and postnatal dev elopment. In the midgestation embryo, GATA-5 transcripts are most abundant in the heart and decrease dramatically in the postnatal heart; in contrast, GATA-5 expression is upregulated in the lung and gut during postnatal deve lopment. Functional studies with recombinant GATA-4, -5, and -6 proteins sh ow that GATA-5 has preferential affinity for a subset of GATA elements foun d on cardiac promoters and differentially activate cardiac gene transcripti on. Structure-function analysis revealed the presence of an activation doma in within the carboxy terminal region of GATA-5 that is essential for trans criptional regulation of target promoters. Linkage analysis localized Gata5 to distal mouse Chromosome (Chr) 2 in a conserved linkage group with genes localized to rat Chr 3q43 and human Chr 20q13.2-q13.3. The results suggest that GATA-5 may have specific downstream targets and that GATA-4, -5, and -6 can only partially substitute for each other in cardiogenesis. Thus, Gat a5 probably plays a specialized evolutionary conserved role in cardiac deve lopment.