Viger Robert S, Guittot Séverine Mazaud, Anttonen Mikko, Wilson David B, Heikinheimo Markku
Ontogeny-Reproduction Research Unit, Room T1-49, CHUQ Research Centre, 2705 Laurier Boulevard, Quebec City, Quebec, Canada G1V 4G2.
Mol Endocrinol. 2008 Apr;22(4):781-98. doi: 10.1210/me.2007-0513. Epub 2008 Jan 3.
The WGATAR motif is a common nucleotide sequence found in the transcriptional regulatory regions of numerous genes. In vertebrates, these motifs are bound by one of six factors (GATA1 to GATA6) that constitute the GATA family of transcriptional regulatory proteins. Although originally considered for their roles in hematopoietic cells and the heart, GATA factors are now known to be expressed in a wide variety of tissues where they act as critical regulators of cell-specific gene expression. This includes multiple endocrine organs such as the pituitary, pancreas, adrenals, and especially the gonads. Insights into the functional roles played by GATA factors in adult organ systems have been hampered by the early embryonic lethality associated with the different Gata-null mice. This is now being overcome with the generation of tissue-specific knockout models and other knockdown strategies. These approaches, together with the increasing number of human GATA-related pathologies have greatly broadened the scope of GATA-dependent genes and, importantly, have shown that GATA action is not necessarily limited to early development. This has been particularly evident in endocrine organs where GATA factors appear to contribute to the transcription of multiple hormone-encoding genes. This review provides an overview of the GATA family of transcription factors as they relate to endocrine function and disease.
WGATAR基序是在众多基因的转录调控区域中发现的常见核苷酸序列。在脊椎动物中,这些基序由构成GATA转录调节蛋白家族的六个因子(GATA1至GATA6)之一结合。尽管最初认为它们在造血细胞和心脏中发挥作用,但现在已知GATA因子在多种组织中表达,在这些组织中它们作为细胞特异性基因表达的关键调节因子。这包括多个内分泌器官,如垂体、胰腺、肾上腺,尤其是性腺。与不同的Gata基因敲除小鼠相关的早期胚胎致死性阻碍了对GATA因子在成体器官系统中所起功能作用的深入了解。现在,通过生成组织特异性敲除模型和其他敲低策略,这一问题正在得到解决。这些方法,加上越来越多的人类GATA相关病理学研究,极大地拓宽了GATA依赖基因的范围,重要的是,已经表明GATA的作用不一定局限于早期发育。这在内分泌器官中尤为明显,其中GATA因子似乎有助于多种激素编码基因的转录。本综述概述了与内分泌功能和疾病相关的GATA转录因子家族。