GATA-6: A zinc finger transcription factor that is expressed in multiple cell lineages derived from lateral mesoderm

GATA-6: A zinc finger transcription factor that is expressed in multiple cell lineages derived from lateral mesoderm
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DOI:
10.1006/dbio.1996.0165
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发表时间:
1996-07-10
影响因子:
2.7
通讯作者:
Parmacek, MS
Parmacek, MS
中科院分区:
生物学3区
文献类型:
--
作者:
Morrisey, EE;Ip, HS;Parmacek, MS

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锌指转录因子的加塔家族成员在几种中胚层来源的细胞谱系的发育中起重要作用。在本报告中描述的研究中,我们已经分离和功能特性的小鼠加塔-6的cDNA和蛋白质,并定义的时间和空间模式的加塔-6基因表达在哺乳动物的发展。加塔-6和GATA-4蛋白在蛋白质氨基末端的脯氨酸富集区上具有高水平的氨基酸序列同一性,该区域在其他加塔家族成员中不保守。加塔-6与心脏特异性心肌肌钙蛋白C(cTnC)转录增强子内功能重要的核蛋白结合位点结合。此外,cTnC启动子增强子可通过加塔-6在非心肌细胞中的过表达而被反式激活。在早期小鼠胚胎发育过程中,加塔-6和-4基因表达的模式是相似的,加塔-6的表达仅限于心前中胚层、胚胎心管和原肠。然而,与呼吸道和泌尿生殖道的血管发生和发育的开始相一致,只有加塔-6基因在动脉平滑肌细胞、发育中的支气管以及泌尿生殖嵴和膀胱中表达。这些数据与其中加塔-6与加塔-4协同作用以在哺乳动物心脏和胃肠道形成期间指导组织特异性基因表达的模型一致,但在动脉系统、膀胱和胚胎肺中编程谱系限制性基因表达中执行独特功能。(C)出版社:Academic Press,Inc.
Members of the GATA family of zinc finger transcription factors play important roles in the development of several mesodermally derived cell lineages. In the studies described in this report, we have isolated and functionally characterized the murine GATA-6 cDNA and protein and defined the temporal and spatial patterns of GATA-6 gene expression during mammalian development. The GATA-6 and -4 proteins share high-level amino acid sequence identity over a proline-rich region at the amino terminus of the protein that is not conserved in other GATA family members. GATA-6 binds to a functionally important nuclear protein binding site within the cardiac-specific cardiac troponin C (cTnC) transcriptional enhancer. Moreover, the cTnC promoter enhancer can be transactivated by overexpression of GATA-6 in noncardiac muscle cells. During early murine embryonic development, the patterns of GATA-6 and -4 gene expression are similar, with expression of GATA-6 restricted to the precardiac mesoderm, the embryonic heart tube, and the primitive gut. However, coincident with the onset of vasculogenesis and development of the respiratory and urogenital tracts, only the GATA-6 gene is expressed in arterial smooth muscle cells, the developing bronchi, and the urogenital ridge and bladder. These data are consistent with a model in which GATA-6 functions in concert with GATA-4 to direct tissue-specific gene expression during formation of the mammalian heart and gastrointestinal tract, but performs a unique function in programming lineage-restricted gene expression in the arterial system, the bladder, and the embryonic lung. (C) 1996 Academic Press, Inc.