Greenbaum Jason A, Parker Stephen C J, Tullius Thomas D
Program in Bioinformatics, Boston University, Boston, Massachusetts 02215, USA.
Genome Res. 2007 Jun;17(6):940-6. doi: 10.1101/gr.5602807.
The completion of the human genome project has fueled the search for regulatory elements by a variety of different approaches. Many successful analyses have focused on examining primary DNA sequence and/or chromatin structure. However, it has been difficult to detect common sequence motifs within the feature of chromatin structure most closely associated with regulatory elements, DNase I hypersensitive sites (DHSs). Considering just the nucleotide sequence and/or the chromatin structure of regulatory elements may neglect a critical feature of what is recognized by the regulatory machinery--DNA structure. We introduce a new computational method to detect common DNA structural motifs in a large collection of DHSs that are found in the ENCODE regions of the human genome. We show that DHSs have common DNA structural motifs that show no apparent sequence consensus. One such structural motif is much more highly enriched in experimentally identified DHSs that are in CpG islands and near transcription start sites (TSSs), compared to DHSs not in CpG islands and farther from TSSs, suggesting that DNA structural motifs may participate in the formation of functional regulatory elements. We propose that studies of the conservation of DNA structure, independent of sequence conservation, will provide new information about the link between the nucleotide sequence of a DNA molecule and its experimentally demonstrated function.
人类基因组计划的完成推动了通过多种不同方法寻找调控元件的研究。许多成功的分析都集中在检查初级DNA序列和/或染色质结构上。然而，在与调控元件最密切相关的染色质结构特征——DNase I超敏感位点（DHSs）中，很难检测到常见的序列基序。仅考虑调控元件的核苷酸序列和/或染色质结构可能会忽略调控机制所识别的关键特征——DNA结构。我们引入了一种新的计算方法，用于在人类基因组ENCODE区域中发现的大量DHSs中检测常见的DNA结构基序。我们发现DHSs具有常见的DNA结构基序，这些基序没有明显的序列一致性。与不在CpG岛且远离转录起始位点（TSSs）的DHSs相比，一种这样的结构基序在位于CpG岛和靠近转录起始位点（TSSs）的实验鉴定的DHSs中富集程度要高得多，这表明DNA结构基序可能参与功能性调控元件的形成。我们提出，独立于序列保守性的DNA结构保守性研究将提供有关DNA分子核苷酸序列与其实验证明的功能之间联系的新信息。
