Ab initio identification of putative human transcription factor binding sites by comparative genomics.
Ab initio identification of putative human transcription factor binding sites by comparative genomics.
复制标题
DOI：
10.1186/1471-2105-6-110
复制
发表时间：
2005-05-02
影响因子：
3
通讯作者：
Caselle M
中科院分区：
文献类型：
--
作者：
Corà D;Herrmann C;Dieterich C;Di Cunto F;Provero P;Caselle M
理解基因表达的转录调控是现代分子生物学最大的挑战之一。转录因子在这一机制中起着核心作用，转录因子通常与位于被调控基因上游区域的特异性短DNA序列基序结合。我们在这里讨论了一种简单而有力的方法来从头识别这些顺式调控基序。我们提出的方法整合了几个要素：人鼠比较，基因组序列的统计分析和共调控的概念。我们将其应用于人类基因组的完整扫描。利用CORG数据库中收集的上游保守序列目录，我们构建了人类和小鼠在其上游区域共享相同的过度代表基序（短DNA序列）的基因集。我们对长度在5到8个核苷酸之间的所有可能的基序进行这种构建，然后过滤结果集，寻找两种类型的共调控证据：首先，我们分析集合中基因的基因本体注释，寻找具有统计意义的共同注释；其次，我们通过微阵列实验分析了这组基因的表达谱，寻找共表达的证据。据推测，通过一个或两个过滤器的集合包含很大一部分共调节基因，因此表征这些集合的上游基序是参与这种调节的TF的结合位点的良好候选者。通过这种方法，我们发现了许多已知的基序和一些新的候选结合位点。我们讨论了一种新的集成算法，用于“从头开始”鉴定人类基因组中转录因子结合位点。该方法基于三个要素：比较基因组学，过度代表性，不同类型的协同调节。该方法应用于人类基因组的全扫描，结果令人满意。
Understanding transcriptional regulation of gene expression is one of the greatest challenges of modern molecular biology. A central role in this mechanism is played by transcription factors, which typically bind to specific, short DNA sequence motifs usually located in the upstream region of the regulated genes. We discuss here a simple and powerful approach for the ab initio identification of these cis-regulatory motifs. The method we present integrates several elements: human-mouse comparison, statistical analysis of genomic sequences and the concept of coregulation. We apply it to a complete scan of the human genome. By using the catalogue of conserved upstream sequences collected in the CORG database we construct sets of genes sharing the same overrepresented motif (short DNA sequence) in their upstream regions both in human and in mouse. We perform this construction for all possible motifs from 5 to 8 nucleotides in length and then filter the resulting sets looking for two types of evidence of coregulation: first, we analyze the Gene Ontology annotation of the genes in the set, searching for statistically significant common annotations; second, we analyze the expression profiles of the genes in the set as measured by microarray experiments, searching for evidence of coexpression. The sets which pass one or both filters are conjectured to contain a significant fraction of coregulated genes, and the upstream motifs characterizing the sets are thus good candidates to be the binding sites of the TF's involved in such regulation. In this way we find various known motifs and also some new candidate binding sites. We have discussed a new integrated algorithm for the "ab initio" identification of transcription factor binding sites in the human genome. The method is based on three ingredients: comparative genomics, overrepresentation, different types of coregulation. The method is applied to a full-scan of the human genome, giving satisfactory results.
登录
查看更多内容
影响因子：
14.9
作者：
DURET, L;DORKELD, F;GAUTIER, C
通讯作者：
GAUTIER, C
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
1.7
作者：
Thijs, G;Marchal, K;Moreau, Y
通讯作者：
Moreau, Y
影响因子：
7
作者：
Sudarsanam, P;Pilpel, Y;Church, GM
通讯作者：
Church, GM
影响因子：
2.9
作者：
LAWRENCE, CE;REILLY, AA
通讯作者：
REILLY, AA