Winkelmann Silke, Klar Martin, Benham Craig, Prashanth Ak, Goetze Sandra, Gluch Angela, Bode Juergen
GBF German Research Center for Biotechnology/Epigenetic Regulation, Mascheroder Weg 1, D-38124 Braunschweig, Germany.
Brief Funct Genomic Proteomic. 2006 Mar;5(1):24-31. doi: 10.1093/bfgp/ell003. Epub 2006 Feb 23.
The conventional string-based bioinformatic methods of genomic sequence analysis are often insufficient to identify DNA regulatory elements, since many of these do not have a recognizable motif. Even in case a sequence pattern is known to be associated with an element it may only partially mediate its function. This suggests that properties not correlated with the details of base sequence contribute to regulation. One of these attributes is the DNA strand-separation potential, known as SIDD (stress-induced duplex destabilization) which facilitates the access of tracking proteins and the formation of local secondary structures. Using the type 1 interferon gene cluster as a paradigm, we demonstrate that the imprints in a SIDD profile coincide with chromatin domain borders and with DNAse I hypersensitive sites to which regulatory potential could be assigned. The approach permits the computer-guided identification of yet unknown, mostly remote sites and the design of artificial elements with predictable properties for multiple applications.
传统的基于字符串的基因组序列分析生物信息学方法往往不足以识别DNA调控元件,因为其中许多元件没有可识别的基序。即使已知某个序列模式与某个元件相关,它也可能只是部分介导其功能。这表明与碱基序列细节不相关的特性有助于调控。其中一个属性是DNA链分离潜力,即所谓的SIDD(应激诱导双链体不稳定),它有助于追踪蛋白的进入以及局部二级结构的形成。以1型干扰素基因簇为范例,我们证明SIDD图谱中的印记与染色质结构域边界以及可赋予调控潜力的DNA酶I超敏位点相吻合。该方法允许通过计算机指导识别未知的、大多是远距离的位点,并设计具有可预测特性的人工元件以用于多种应用。