Genome-wide analysis of regions similar to promoters of histone genes.
Genome-wide analysis of regions similar to promoters of histone genes.
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DOI：
10.1186/1752-0509-4-s1-s4
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发表时间：
2010-05-28
影响因子：
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通讯作者：
Liu JS
中科院分区：
文献类型：
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作者：
Chowdhary R;Bajic VB;Dong D;Wong L;Liu JS
本研究的目的是：i）建立人类组蛋白编码基因启动子的计算模型（简称组蛋白基因），参与各种关键细胞过程的一类重要基因，ii）使用如此开发的模型来鉴定整个人类基因组中具有与组蛋白基因启动子相似结构的区域;这样的区域可以代表可能与组蛋白基因共调节的基因的潜在基因组调节区域，例如启动子，和iii/以这种方式鉴定具有与组蛋白基因共调节的高可能性的基因。我们成功地开发了一个组蛋白启动子模型，使用全面收集的组蛋白基因。基于留一法交叉验证检验，该模型产生了良好的预测准确性（94.1%的灵敏度，92.6%的特异性，和92.8%的阳性预测值）。我们使用这个模型来预测整个基因组中与组蛋白基因启动子共享相似启动子结构的一些基因。因此，我们假设，这些预测的基因可以与组蛋白基因共调节。这一假设与现有的基因表达、基因本体和途径数据很好地匹配。结合上述基因的启动子，我们发现了大量与组蛋白启动子结构相似的基因间区。这项研究是迄今为止在全基因组范围内对人类组蛋白基因启动子进行的最全面的计算分析之一。我们的分析表明，一些其他的人类基因，共享一个高度相似的启动子结构与组蛋白基因，因此很可能是共调节，因此共表达，与组蛋白基因。我们还发现，在整个基因组中存在大量的基因间区，它们的结构类似于组蛋白基因的启动子。这些区域可能是尚未鉴定的基因的启动子，或者可能代表参与组蛋白和组蛋白共调节基因转录起始的调控的远程控制区域。虽然这些假说仍有待验证，但我们相信这些假说为研究人员进一步探索人类组蛋白基因和人类基因组的调控提供了有用的资源。值得注意的是，即使在今天，人类基因组的调控区域在很大程度上仍然没有注释，这项研究试图补充我们对组蛋白调控区域的理解。
The purpose of this study is to: i) develop a computational model of promoters of human histone-encoding genes (shortly histone genes), an important class of genes that participate in various critical cellular processes, ii) use the model so developed to identify regions across the human genome that have similar structure as promoters of histone genes; such regions could represent potential genomic regulatory regions, e.g. promoters, of genes that may be coregulated with histone genes, and iii/ identify in this way genes that have high likelihood of being coregulated with the histone genes. We successfully developed a histone promoter model using a comprehensive collection of histone genes. Based on leave-one-out cross-validation test, the model produced good prediction accuracy (94.1% sensitivity, 92.6% specificity, and 92.8% positive predictive value). We used this model to predict across the genome a number of genes that shared similar promoter structures with the histone gene promoters. We thus hypothesize that these predicted genes could be coregulated with histone genes. This hypothesis matches well with the available gene expression, gene ontology, and pathways data. Jointly with promoters of the above-mentioned genes, we found a large number of intergenic regions with similar structure as histone promoters. This study represents one of the most comprehensive computational analyses conducted thus far on a genome-wide scale of promoters of human histone genes. Our analysis suggests a number of other human genes that share a high similarity of promoter structure with the histone genes and thus are highly likely to be coregulated, and consequently coexpressed, with the histone genes. We also found that there are a large number of intergenic regions across the genome with their structures similar to promoters of histone genes. These regions may be promoters of yet unidentified genes, or may represent remote control regions that participate in regulation of histone and histone-coregulated gene transcription initiation. While these hypotheses still remain to be verified, we believe that these form a useful resource for researchers to further explore regulation of human histone genes and human genome. It is worthwhile to note that the regulatory regions of the human genome remain largely un-annotated even today and this study is an attempt to supplement our understanding of histone regulatory regions.