Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation.

Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation.
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DOI:
10.1093/nar/gkn948
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发表时间:
2009-02
影响因子:
14.9
通讯作者:
Bortoluzzi S
Bortoluzzi S
中科院分区:
生物学2区
文献类型:
--
作者:
Coppe A;Ferrari F;Bisognin A;Danieli GA;Ferrari S;Bicciato S;Bortoluzzi S

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共表达的基因可以处于类似的基于启动子和/或基于位置的调节之下。尽管人类基因的表达、位置和功能的数据是可用的,但它们的真正整合仍然对计算生物学构成挑战,阻碍了调控机制的识别。我们对骨髓细胞中表达的基因的基因组位置、功能注释和启动子进行了综合分析。启动子分析是通过一种新颖的多步骤方法进行的,用于发现与背景模型相比,在选定的一组启动子中推定的调控元件,即过度表达的基序。转录、结构和功能数据的结合使得能够鉴定与人类基因组区域中共表达和共定位的基因组相关的启动子组。对在骨髓细胞分化中共表达并在基因组中共定位的 26 组基因进行基序发现的应用表明,共表达和共定位基因的启动子中比简单共表达基因(CEG)的启动子中存在更多过度表达的基序。鉴定出与已知转录因子的结合序列相似、沿着启动子序列非均匀分布和/或出现在高度共表达的基因子集中的基序。共表达和共定位的基因集被分组在两个共表达的基因组元区域中,假定代表高水平表达调控的功能域。
Genes co-expressed may be under similar promoter-based and/or position-based regulation. Although data on expression, position and function of human genes are available, their true integration still represents a challenge for computational biology, hampering the identification of regulatory mechanisms. We carried out an integrative analysis of genomic position, functional annotation and promoters of genes expressed in myeloid cells. Promoter analysis was conducted by a novel multi-step method for discovering putative regulatory elements, i.e. over-represented motifs, in a selected set of promoters, as compared with a background model. The combination of transcriptional, structural and functional data allowed the identification of sets of promoters pertaining to groups of genes co-expressed and co-localized in regions of the human genome. The application of motif discovery to 26 groups of genes co-expressed in myeloid cells differentiation and co-localized in the genome showed that there are more over-represented motifs in promoters of co-expressed and co-localized genes than in promoters of simply co-expressed genes (CEG). Motifs, which are similar to the binding sequences of known transcription factors, non-uniformly distributed along promoter sequences and/or occurring in highly co-expressed subset of genes were identified. Co-expressed and co-localized gene sets were grouped in two co-expressed genomic meta-regions, putatively representing functional domains of a high-level expression regulation.
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