Structural characterization of the mouse Hfh4 gene, a developmentally regulated forkhead family member

Structural characterization of the mouse Hfh4 gene, a developmentally regulated forkhead family member
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DOI:
10.1006/geno.1997.4970
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发表时间:
1997-11-01
期刊:
影响因子:
4.4
通讯作者:
White, RA
White, RA
中科院分区:
生物学3区
文献类型:
--
作者:
Brody, SL;Hackett, BP;White, RA

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肝细胞核因子-3/叉头同源4(HfH-4)是一个叉头/翼状螺旋转录因子家族成员,在发育和成人肺、脉络丛、睾丸和输卵管中具有独特的基因表达的时空模式。为了进一步鉴定HfH-4,分离和分析了小鼠基因组克隆。Hfh4基因位于小鼠11号染色体末端的5.5kb区域,由两个外显子和一个内含子组成。与大多数叉头基因不同,DNA结合域被划分为两个外显子,内含子位置正好对应于涉及两个已知人类叉头同源物的基因易位的位置。在一个不包含TATA或CAAT盒的富含G+C的序列中发现了多个假定的转录起始点。在2.1kb的5‘侧翼序列中,有三个相同的E盒和多个可能的转录因子结合位点。含有报告基因的Hfh4 5‘侧翼序列的载体在肺上皮细胞中具有启动子活性,而在上皮样纤维肉瘤细胞中不具有启动子活性,这表明该5’侧翼序列可以作为启动子发挥作用,并具有适当的细胞类型特异性。(C)1997年学术出版社。
Hepatocyte nuclear factor-3/forkhead homologue 4 (HFH-4) is a forkhead/winged-helix transcription factor family member that has a unique temporal and spatial pattern of gene expression in the developing and adult lung, choroid plexus, testis, and oviduct. To characterize HFH-4 further, mouse genomic clones were isolated and analyzed. The Hfh4 gene is encoded on a 5.5-kb region located on the distal end of mouse chromosome 11 and consists of two exons and one intron. Unlike most forkhead genes, the DNA binding domain is divided between two exons, and the intron position corresponds precisely to the site of gene translocations involving two known human forkhead homologues. Multiple putative transcription start sites are identified in a G+C-rich sequence that does not contain TATA or CAAT boxes. Within 2.1 kb of 5' flanking sequence are three identical E boxes and multiple putative transcription factor binding sites. Transfection of plasmids containing Hfh4 5' flanking sequence linked to a reporter gene results in promoter activity in lung epithelial cells but not in epithelial-like fibrosarcoma cells, suggesting that this 5' flanking sequence can function as a promoter with the proper cell-type specificity. (C) 1997 Academic Press.