title: Structure of the human Nkx2.1 gene.
abstract: 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 Nkx2.1 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.
authors.affiliation: Department of Pediatrics, Women's and Children's Hospital, University of Southern California, School of Medicine, Los Angeles 90033, USA.
authors.forename: H
authors.initials: H
authors.lastname: Hamdan
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: C
authors.initials: C
authors.lastname: Jones
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: R
authors.initials: R
authors.lastname: deLemos
authors.forename: P
authors.initials: P
authors.lastname: Minoo
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012689:Sequence Homology, Nucleic Acid; D013961:Thyroid Gland / Q000378:metabolism; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D018076:DNA, Complementary; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors