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Title: Transforming growth factor-β3 gene structure and evolution
Author: Dey, Bhakta Ranjan
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1991
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Transforming growth factor-β (TGF-β) is a multifunctional regulator of cellular proliferation and differentiation. It has been suggested that members of the TGF-β gene family also control differentiation and morphogenesis in embryonic developments. Since the chicken embryogenesis has been so extensively studied, we chose to clone the chicken TGF-β3 gene to facilitate a more detailed analysis of the developmental role of TGF-βs. We have cloned and characterised the chicken TGF-β3 gene and its flanking regions from a White Leghorn chicken genomic library packaged into λEMBL3 using chicken TGF-β3 exon specific oligonucleotide probes. We have determined the gene structure from overlapping genomic clones. The chicken TGF-β3gene contains 7 exons and 6 introns, spanning 15.6kb of genomic DNA. The intron/exon organisation was initially characterised on the basis of Southern blot analysis using exon specific oligonucleotide probe(s) and subsequently confirmed by DNA sequencing. We have also characterised the chicken TGF-β3 promoter. The promoter is very GC-rich and lies within an extensive CpG island of approximately 2400 nucleotides. The 5'-untranslated region is 467 bp, in length shorter than that found in the human TGF-β3 gene (1356 bp). A comparison of the 5'-flanking regions from the chicken and human TGF-β3 genes revealed two regions of sequence homology: an 86 bp sequence surrounding the transcription start and a 156 bp sequence in the 5'-untranslatedregion. The conserved region near the transcription start contains short sequences that resemble TATA box, cAMP responsive element (CRE), and AP-2 consensus motifs. These are cis acting sequences we believe may be important for promoter activity. The conserved region in the 5'-untranslated region is also present in chicken, mouse, porcine and human TGF-β3genes and may have a regulatory role. The chicken TGF-β3 promoter has no sequence homology with either TGD-β2 promoters. We do, however, find some striking similarities between TGF-β2 and TGF-β3 promoters, including the conserved regulatory sequences of TATA box, CRE and AP-2 sequence motifs near the transcription initiation site. A computer assisted search of the chicken TGF-β3 gene nucleotide sequence identified several other potential binding sites for known regulatory proteins. Besides the above, these include the recognition sequences for the transcription factors TFIID, MyoDl, Spl, PEA3, Krox-24 and GRE. Further studies on TGF-β3 gene regulation should determine the significance of these regulatory protein binding sites. The 3'-untranslated region of the gene is approximately 956 bp in length. A sequence comparison of chicken TGF-β3 3' flanking sequence with the published cDNA sequences of mouse, porcine and human TGF-β3 reveals a highly conserved 84 bp segment around the polyadenylation signal.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available