Molecular characterization and physiological regulation of a TATA-less gene encoding chicken gastrin.
Molecular characterization and physiological regulation of a TATA-less gene encoding chicken gastrin.
复制标题
编码鸡胃泌素的无 TATA 基因的分子特征和生理调控。
DOI：
10.1111/j.1432-1033.1995.tb20580.x
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Dimaline,R
中科院分区：
文献类型：
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作者：
Wu,SV;Walsh,JH;Campbell,BJ;Dimaline,R
禽胃泌素是一种胃酸促分泌素，但在结构上与哺乳动物胆囊收缩素更密切相关，而后者在功能上与胃泌素不同。这种明显异常的结构/活性关系提出了重要的问题，了解调控肽的演变和控制其表达的机制。为了阐明可能的机制，我们已经确定了6.5 kbBamHI基因组DNA片段的序列，其中包括整个禽胃泌素转录单位。通过锚定PCR确定的完整cDNA序列编码105个氨基酸的前体。保守的一级氨基酸结构仅限于决定生物活性的十肽和翻译后加工的必需位点。然而，值得注意的是，基因组调控区和内含子，不像以前报道的任何胃泌素/胆囊收缩素基因。禽胃泌素基因不包含可识别的TATA‐box基序，这是该基因家族的独特特征，但在转录起始位点的上游有一个富含G+C‐的区域，以及一个Z-DNA嘌呤-嘧啶重复序列。此外，鸟类胃泌素基因的生理调节与哺乳动物中观察到的明显不同，因为没有胃窦生长抑素的重要局部旁分泌下调;相反，证明了激素调节的证据。这些数据表明，基因组调控元件内的调节肽家族，如胃泌素/胆囊收缩素家族，和生理控制机制，在进化过程中不保守，即使生物学上重要的氨基酸序列信息被保留。
Avian gastrin is a gastric acid secretagogue, but is structurally more closely related to mammalian cholecystokinin, which is functionally distinct from gastrin. This apparently anomalous structure/activity relationship raises important issues for understanding the evolution of regulatory peptides and the mechanisms that control their expression. To clarify the possible mechanisms, we have determined the sequence of a 6.5‐kbBamHI genomic DNA fragment that includes the entire avian gastrin transcriptional unit. The complete cDNA sequence, determined by anchored PCR, encoded a precursor of 105 amino acids. Conserved primary amino acid structures were limited to a decapeptide determining biological activity, and essential sites for post‐translational processing. Significantly, however, the genomic regulatory regions, and introns, were unlike those of any previously reported gastrin/cholecystokinin gene. The avian gastrin gene contained no recognizable TATA‐box motif, a feature unique to this gene family, but had a G+C‐rich region immediately upstream of the transcription initiation site, and a Z‐DNA purine‐pyrimidine repeat sequence. Moreover, physiological regulation of the avian gastrin gene differed markedly from that observed in mammals, in that the important local paracrine downregulation by antral somatostatin was absent; instead, evidence for a hormonal regulation was demonstrated. The data indicate that genomic regulatory elements within regulatory peptide families such as the gastrin/cholecystokinin family, and mechanisms of physiological control, are not conserved during evolution, even though biologically important amino acid sequence information is retained.