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dmyc启动子及调控区域的研究

Investigation of dmyc Promoter and Regulatory Regions.

作者信息

Kharazmi Jasmine, Moshfegh Cameron

机构信息

Bio-Technopark Zurich, Molecular Biology Laboratory, Zurich, Switzerland. ; Institute of Molecular Life Sciences, University of Zurich-Irchel, Zurich, Switzerland.

出版信息

Gene Regul Syst Bio. 2013 May 15;7:85-102. doi: 10.4137/GRSB.S10751. Print 2013.

Abstract

Products of the myc gene family integrate extracellular signals by modulating a wide range of their targets involved in cellular biogenesis and metabolism; the purpose of this integration is to regulate cell death, proliferation, and differentiation. However, understanding the regulation of myc at the transcription level remains a challenge. We performed rapid amplification of dmyc cDNA ends (5' RACE) and mapped the transcription start site at P1 promoter, 18 base pairs upstream of the start of the known EST GM01143 and within the 5' UTR. Our data show that the first TATA box, previously computationally predicted, is utilized to generate dmyc full length mRNA. The largest transcript contains all three exons, generated after the removal of the introns by constitutively regulated splicing events. Further investigation of Downstream Promoter Element (DPE) was achieved by studying lacZ reporter activity; investigation revealed that this element and its upstream cluster of binding sites are required for the dmyc intron 2 activity. These findings may provide valuable tools for further analysis of dmyc cis-elements.

摘要

myc基因家族的产物通过调节参与细胞生物合成和代谢的多种靶标来整合细胞外信号;这种整合的目的是调节细胞死亡、增殖和分化。然而,在转录水平上理解myc的调控仍然是一个挑战。我们进行了dmyc cDNA末端快速扩增(5' RACE),并将转录起始位点定位在P1启动子处,该启动子位于已知EST GM01143起始位点上游18个碱基对处,且在5' UTR内。我们的数据表明,先前通过计算预测的第一个TATA盒被用于生成dmyc全长mRNA。最大的转录本包含所有三个外显子,这些外显子是通过组成性调控的剪接事件去除内含子后产生的。通过研究lacZ报告基因活性对下游启动子元件(DPE)进行了进一步研究;研究表明,该元件及其上游结合位点簇是dmyc内含子2活性所必需的。这些发现可能为进一步分析dmyc顺式元件提供有价值的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31a1/3663572/50132e0b8b6d/grsb-7-2013-085f1.jpg

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