A Transcriptional Enhancer from the Coding Region of ADAMTS5
A Transcriptional Enhancer from the Coding Region of ADAMTS5
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DOI：
10.1371/journal.pone.0002184
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发表时间：
2008-05-14
期刊：
影响因子：
3.7
通讯作者：
Liu, Xuedong
中科院分区：
文献类型：
--
作者：
Barthel, Kristen K. B.;Liu, Xuedong
背景资料：人类基因组编码的基因只有25,000个，因此无法解释表型的复杂性，这是后基因组时代最大的惊喜之一。然而，越来越多的证据表明，转录调控可能在很大程度上负责这种观察到的哺乳动物的复杂性。因此，有一个强大的驱动力，以确定哺乳动物基因组中的顺式调控区域，以了解这些地区，包括其基因组分布的统一原则。虽然已经开发了一些系统的方法，这些都折扣coding sequence.Methodology/Principal Findings：使用计算工具PRI（模式定义的监管岛），它不掩盖编码序列，我们确定了一个监管区域与基因ADAMTS 5，包括整个的基本编码外显子2。我们证明，通过结合染色质免疫沉淀和报告基因的研究，该区域不仅可以结合肌源性转录因子MYOD和myogenin和E-蛋白HEB，但也可以作为一个非常强大的肌源性转录enhancer.Conclusions/Significance：因此，我们报告的识别和详细的表征的外显子增强子。最终，这就引出了一个有趣的问题：为什么进化在序列的功能分配上如此吝啬。
Background: The revelation that the human genome encodes only similar to 25,000 genes and thus cannot account for phenotypic complexity has been one of the biggest surprises in the post-genomic era. However, accumulating evidence suggests that transcriptional regulation may be in large part responsible for this observed mammalian complexity. Consequently, there has been a strong drive to locate cis-regulatory regions in mammalian genomes in order to understand the unifying principles governing these regions, including their genomic distribution. Although a number of systematic approaches have been developed, these all discount coding sequence.Methodology/Principal Findings: Using the computational tool PRI (Pattern-defined Regulatory Islands), which does not mask coding sequence, we identified a regulatory region associated with the gene ADAMTS5 that encompasses the entirety of the essential coding exon 2. We demonstrate through a combination of chromatin immunoprecipitation and reporter gene studies that this region can not only bind the myogenic transcription factors MYOD and myogenin and the E-protein HEB but can also function as a very strong myogenic transcriptional enhancer.Conclusions/Significance: Thus, we report the identification and detailed characterization of an exonic enhancer. Ultimately, this leads to the interesting question of why evolution would be so parsimonious in the functional assignment of sequence.