Structure of the human Nkx2.1 gene

被引:56
作者
Hamdan, H [1 ]
Liu, HB [1 ]
Li, CG [1 ]
Jones, C [1 ]
Lee, M [1 ]
deLemos, R [1 ]
Minoo, P [1 ]
机构
[1] Univ So Calif, Sch Med, Womens & Childrens Hosp, Dept Pediat, Los Angeles, CA 90033 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION | 1998年 / 1396卷 / 03期
关键词
Nkx2.1; lung development; homeoprotein; genomic clone; promoter domain;
D O I
10.1016/S0167-4781(97)00210-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
NKX2.1 is a member of the NK2 family of homeodomain-containing transcriptional factors which binds to and activates the promoters of thyroid and pulmonary epithelial genes. We have cloned and sequenced twelve human lung Nkx2.1 cDNAs. To elucidate the origin of Nkr2.1 transcripts, we also cloned and sequenced a 12 kb human Nkx2.1 genomic clone. Alignment of cDNA sequences with the genomic clone showed that contrary to previous reports, the human Nkx2.1 gene is organized into three exons and two introns. The newly discovered exon I contains an ATG codon that falls in frame with the previously identified Nkx2.1 initiator ATG codon on one of the cDNAs, designated 5E. Northern blot analysis shows that an mRNA of approximately 2.5 kb in size, homologous to 5E, is expressed in both lung and thyroid, The deduced amino acid sequence of the longest open reading frame on 5E is identical to NKX2.1 with the exception of a 30 amino acid N-terminal extension. Coupled in vitro transcription/translation of the 5E cDNA confirms that the open reading frame is translated into a contiguous polypeptide of 44 kDa. Analysis of Nkx2.1 genomic DNA fragments suggest that at least two independent regions, one within the first intron and the other 5' of the first exon may mediate the basal promoter activity of the Nkx2.1 gene in lung epithelial cells. (C) 1998 Elsevier Science B.V.
引用
收藏
页码:336 / 348
页数:13
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