Nemer G, Qureshi S T, Malo D, Nemer M
Laboratoire de développement et différenciation cardiaques, Institut de recherches cliniques de Montréal, 110 des Pins Ouest, Montréal, Québec, Canada H2W 1R7.
Mamm Genome. 1999 Oct;10(10):993-9. doi: 10.1007/s003359901146.
The GATA family of zinc finger proteins are transcriptional regulators with critical functions in lineage differentiation and embryonic development. Based on structural and expression pattern comparisons, the GATA proteins have been subdivided into two groups. The first subgroup consists of GATA-1, -2, and -3, which are all highly expressed in the hematopoietic system, whereas GATA-4, -5, and -6 are present essentially in the heart and gut. We have isolated and functionally characterized the rat GATA-5 cDNA, which encodes 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 development. 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 development. Functional studies with recombinant GATA-4, -5, and -6 proteins show that GATA-5 has preferential affinity for a subset of GATA elements found on cardiac promoters and differentially activate cardiac gene transcription. Structure-function analysis revealed the presence of an activation domain within the carboxy terminal region of GATA-5 that is essential for transcriptional 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, Gata5 probably plays a specialized evolutionary conserved role in cardiac development.
锌指蛋白的GATA家族是转录调节因子，在谱系分化和胚胎发育中具有关键功能。基于结构和表达模式的比较，GATA蛋白已被细分为两组。第一亚组由GATA-1、-2和-3组成，它们在造血系统中均高度表达，而GATA-4、-5和-6主要存在于心脏和肠道中。我们已经分离并对大鼠GATA-5 cDNA进行了功能表征，该cDNA编码一种45 kDa的蛋白质，与两栖类、鸟类和鼠类同源物的同源性分别为71%、73%和97%。Northern印迹分析表明，大鼠GATA-5在胚胎期和出生后发育过程中呈动态表达模式。在妊娠中期胚胎中，GATA-5转录本在心脏中最为丰富，在出生后的心脏中急剧减少；相反，GATA-5在出生后发育过程中在肺和肠道中的表达上调。对重组GATA-4、-5和-6蛋白的功能研究表明，GATA-5对心脏启动子上发现的一部分GATA元件具有优先亲和力，并能差异激活心脏基因转录。结构-功能分析揭示了GATA-5羧基末端区域存在一个激活域，这对于靶启动子的转录调控至关重要。连锁分析将Gata5定位到小鼠远端染色体（Chr）2上的一个保守连锁群中，该连锁群中的基因定位于大鼠Chr 3q43和人类Chr 20q13.2-q13.3。结果表明，GATA-5可能有特定的下游靶点，并且GATA-4、-5和-6在心脏发生过程中只能部分相互替代。因此，Gata5可能在心脏发育中发挥专门的进化保守作用。
