预测血清反应因子（SRF）共调控因子及构建调控网络

发布时间：2018-11-22 07:53

【摘要】：转录因子与顺式元件的正确识别是调控基因表达的关键，深入研究二者的内在关系对构建靶基因调控网络极为重要。血清反应因子SRF是普遍存在于哺乳动物中的多功能转录因子,其DNA结合位点CC(AT)6GG即CArG元件在哺乳动物进化史上极为保守，故顺式元件CArG的突变可能是产生SRF不当调控并导致许多疾病发生的重要原因。常规序列分析方法寻找功能CArG元件的假阳性较高，制约了SRF和其共调控因子对靶基因调控网络的构建。本研究从人类全基因组转录起始位点上下游2000bp的序列上，搜索至多允许一个突变的CArG元件，利用46个脊椎动物中的全基因组比对数据，找出人基因组上转录起始位点上下游2000bp范围内保守CArG元件4744个。再结合表达量数据（正常VS沉默SRF），进一步确认特异实验条件下SRF的潜在靶基因652个。为构建调控网络，我们对SRF靶基因按功能进行聚类，，有相同或相似功能的基因被聚在一个类中。取每个功能类的中靶基因上CArG元件上下游500bp的序列，预测可能与SRF进行共调控的转录因子，为进一步筛选出在特异实验条件下起调控作用的转录因子，利用惩罚多变量回归筛选出每个功能类中起主要作用的转录因子，发现不同功能类基因中SRF可能会与不同的共调控因子相互作用来调控该功能类的转录，不同功能类基因中SRF的调控模式可能是不同的。最后，我们用预测出的SRF靶基因及共调控因子,构建了不同功能类中SRF和共调控因子对其靶基因的调控网络。
[Abstract]:The correct recognition of transcription factors and cis-elements is the key to the regulation of gene expression. It is very important to study the relationship between transcription factors and cis-elements in the construction of target gene regulatory networks. Serum response factor (SRF) is a multifunctional transcription factor in mammals. Its DNA binding site, CC (AT) 6GG, or CArG element, is highly conserved in mammalian evolutionary history. Therefore, the mutation of cis-element CArG may be an important reason for the improper regulation of SRF and the occurrence of many diseases. The detection of false positive of functional CArG elements by routine sequence analysis method restricts the construction of target gene regulatory network by SRF and its co-regulatory factors. In this study, we searched for at most one mutated 2000bp element from the upstream and downstream 2000bp sequences of the entire human genome, using genomic alignment data from 46 vertebrates. A total of 4 744 conserved CArG elements were identified in the upstream and downstream 2000bp range of transcription initiation sites in the human genome. Combined with the expression data (normal VS silencing SRF),) further identified 652 potential target genes of SRF under specific experimental conditions. In order to construct regulatory networks, SRF target genes are clustered according to their functions, and genes with the same or similar functions are clustered in one class. The upstream and downstream 500bp sequences of CArG elements were sequenced from the midtarget genes of each functional class, and the transcription factors that might be coregulated with SRF were predicted. In order to further screen the transcription factors that play a regulatory role in specific experimental conditions, The transcription factors that play a major role in each functional class were screened by using penalty multivariate regression. It was found that SRF in different functional class genes might interact with different co-regulatory factors to regulate transcription of the functional class. The regulatory patterns of SRF in different functional genes may be different. Finally, using the predicted target genes and co-regulatory factors of SRF, we constructed the regulatory networks of SRF and co-regulatory factors to target genes in different functional classes.
【学位授予单位】：西北农林科技大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R346;O242.1

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