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首页> 外文期刊>Genomics >Short ultraconserved promoter regions delineate a class of preferentially expressed alternatively spliced transcripts.
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Short ultraconserved promoter regions delineate a class of preferentially expressed alternatively spliced transcripts.

机译：短的超保守启动子区域描绘了一类优先表达的选择性剪接的转录本。

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摘要

Ultraconservation has been variously defined to describe sequences that have remained identical or nearly so over long periods of evolution to a degree that is higher than expected for sequences under typical constraints associated with protein-coding sequences, splice sites, or transcription factor binding sites. Most intergenic ultraconserved elements (UCE) appear to be tissue-specific enhancers, whereas another class of intragenic UCEs is involved in regulation of gene expression by means of alternative splicing. In this study we define a set of 2827 short ultraconserved promoter regions (SUPR) in 5 kb upstream regions of 1268 human protein-coding genes using a definition of 98% identity for at least 30 bp in 7 mammalian species. Our analysis shows that SUPRs are enriched in genes playing a role in regulation and development. Many of the genes having a SUPR-containing promoter have additional alternative promoters that do not contain SUPRs. Comparison of such promoters by CAGE tag, EST, and Solexa read analysis revealed that SUPR-associated transcripts show a significantly higher mean expression than transcripts associated with non-SUPR-containing promoters. The same was true for the comparison between all SUPR-associated and non-SUPR-associated transcripts on a genome-wide basis. SUPR-associated genes show a highly significant tendency to occur in regions that are also enriched for intergenic short ultraconserved elements (SUE) in the vicinity of developmental genes. A number of predicted transcription factor binding sites (TFBS) are overrepresented in SUPRs and SUEs, including those for transcription factors of the homeodomain family, but in contrast to SUEs, SUPRs are also enriched in core-promoter motifs. These observations suggest that SUPRs delineate a distinct class of ultraconserved sequences.
机译：已经对超保守进行了各种定义，以描述在长期进化过程中保持相同或几乎如此的序列，其程度高于在与蛋白质编码序列，剪接位点或转录因子结合位点相关的典型限制下的序列预期的程度。大多数基因间超保守元件（UCE）似乎是组织特异性增强子，而另一类基因内UCE通过替代剪接参与基因表达的调控。在这项研究中，我们使用7种哺乳动物物种中至少30 bp的98％一致性定义，在1268个人类蛋白质编码基因的5 kb上游区域中定义了一组2827个短超保守启动子区域（SUPR）。我们的分析表明，SUPRs富含在调控和发育中发挥作用的基因。许多具有包含SUPR的启动子的基因具有不包含SUPR的其他替代启动子。通过CAGE标签，EST和Solexa阅读分析对此类启动子进行比较，发现与不包含SUPR的启动子相关的转录本相比，SUPR相关的转录本表现出明显更高的平均表达。对于基于基因组范围的所有SUPR相关转录本和非SUPR相关转录本之间的比较，也是如此。 SUPR相关基因显示出高度显着的趋势，该趋势发生在发育基因附近也富含基因间短超保守元件（SUE）的区域。 SUPR和SUE中有许多预测的转录因子结合位点（TFBS），其中包括同源域家族转录因子的结合位点过高，但与SUE相比，SUPR也富含核心启动子基序。这些观察结果表明SUPR描述了不同类别的超保守序列。

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