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Gtx:一种新的含小鼠同源异型框基因,在脑胶质细胞和睾丸生殖细胞中特异性表达,在体外对血清诱导型启动子具有转录抑制活性。

Gtx: a novel murine homeobox-containing gene, expressed specifically in glial cells of the brain and germ cells of testis, has a transcriptional repressor activity in vitro for a serum-inducible promoter.

作者信息

Komuro I, Schalling M, Jahn L, Bodmer R, Jenkins N A, Copeland N G, Izumo S

机构信息

Molecular Medicine Division, Beth Israel Hospital, Boston, MA.

出版信息

EMBO J. 1993 Apr;12(4):1387-401. doi: 10.1002/j.1460-2075.1993.tb05783.x.

Abstract

Although it is likely that a highly complex network of transcription factors acts in concert during mammalian brain development, relatively few such genes have been characterized to date. We describe here a novel murine homeobox gene, denoted Gtx, which in adult animals is specifically expressed within glial cells of the central nervous system, including the forebrain, and in germ cells of the testis. Gtx resides on chromosome 7 and does not cosegregate with any previously mapped homeobox gene. The amino acid sequence of the predicted protein encoded by Gtx is highly divergent from that of any other known homeobox genes. The Gtx homeodomain contains unique residues at positions predicted to contact DNA bases. It did not bind to known target sites for other homeobox genes in vitro but bound with high affinity to the MEF-2 motif, a binding site for the serum response factor-related proteins. GTX efficiently competed with RSRF to bind the MEF-2 element in vitro. Co-transfection of Gtx prevented the serum-induced activation of the MEF-2-containing reporter genes. Although the true biological role of Gtx is not known, these results suggest that Gtx is a novel cell-type specific homeobox gene that has the potential to act as a transcriptional repressor for a subset of serum-inducible genes.

摘要

尽管在哺乳动物大脑发育过程中,可能有一个高度复杂的转录因子网络协同发挥作用,但迄今为止,已被鉴定的此类基因相对较少。我们在此描述一种新的小鼠同源盒基因,命名为Gtx,在成年动物中,它特异性表达于中枢神经系统的神经胶质细胞内,包括前脑,以及睾丸的生殖细胞中。Gtx位于7号染色体上,与任何先前定位的同源盒基因都不共分离。Gtx编码的预测蛋白的氨基酸序列与任何其他已知同源盒基因的序列高度不同。Gtx同源结构域在预测与DNA碱基接触的位置含有独特的残基。它在体外不与其他同源盒基因的已知靶位点结合,但与MEF-2基序(血清反应因子相关蛋白的结合位点)具有高亲和力结合。GTX在体外能有效竞争RSRF与MEF-2元件的结合。共转染Gtx可阻止血清诱导的含MEF-2报告基因的激活。尽管Gtx的真正生物学作用尚不清楚,但这些结果表明,Gtx是一种新的细胞类型特异性同源盒基因,有可能作为一部分血清诱导基因的转录抑制因子发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7be/413350/5d2b8cd05be6/emboj00076-0135-a.jpg

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