Microarray and comparative genomics-based identification of genes and gene regulatory regions of the mouse immune system
Microarray and comparative genomics-based identification of genes and gene regulatory regions of the mouse immune system
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DOI：
10.1186/1471-2164-5-82
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发表时间：
2004-10-25
期刊：
影响因子：
4.4
通讯作者：
Aronow, BJ
中科院分区：
文献类型：
--
作者：
Hutton, JJ;Jegga, AG;Aronow, BJ
背景：在这项研究中，我们建立并挖掘了一个由 65 个不同小鼠组织组成的基因表达数据库，用于寻找在免疫组织和细胞类型中优先表达的基因。使用表达模式标准，我们鉴定了 360 个在胸腺、脾脏、外周血单核细胞、淋巴结（未刺激或刺激）或体外激活的 T 细胞中优先表达的基因。 结果：基于所有组织或仅免疫组织的表达模式相似性形成的基因簇与趋化因子介导的反应、抗原加工、受体相关信号转导和转录调控等免疫过程具有高度显着的关联。一般过程，例如复制和细胞周期控制。簇内基因相关性涉及已知基因的已知关联，以及描述不明确的基因的免疫过程相关作用。为了表征具有相似表达模式的基因的调控机制和顺式元件，我们使用了基于比较基因组学的顺式元件分析工具的新版本来识别多个基因之间具有组成相似性的顺式元件簇。几个簇包含共享 5-6 个顺式元件的基因，其中包括 ETS 和锌指结合位点。顺式元件 AP2 EGRF ETSF MAZF SP1F ZF5F 和 AREB ETSF MZF1 PAX5 STAT 在胸腺表达组中共享； AP4R E2FF EBOX ETSF MAZF SP1F ZF5F 和 CREB E2FF MAZF PCAT SP1F STAT 顺式簇出现在激活的 T 细胞中； CEBP CREB NFKB SORY 和 GATA NKXH OCTI RBIT 发生在受刺激的淋巴结中。结论：本研究展示了一系列分析方法，这些方法可以揭示参与免疫系统分化、维持和功能的基因和调控元件。它们的多态性或突变可能会对免疫系统功能产生不利影响。
Background: In this study we have built and mined a gene expression database composed of 65 diverse mouse tissues for genes preferentially expressed in immune tissues and cell types. Using expression pattern criteria, we identified 360 genes with preferential expression in thymus, spleen, peripheral blood mononuclear cells, lymph nodes (unstimulated or stimulated), or in vitro activated T-cells.Results: Gene clusters, formed based on similarity of expression-pattern across either all tissues or the immune tissues only, had highly significant associations both with immunological processes such as chemokine-mediated response, antigen processing, receptor-related signal transduction, and transcriptional regulation, and also with more general processes such as replication and cell cycle control. Within-cluster gene correlations implicated known associations of known genes, as well as immune process-related roles for poorly described genes. To characterize regulatory mechanisms and cis-elements of genes with similar patterns of expression, we used a new version of a comparative genomics-based cis-element analysis tool to identify clusters of cis-elements with compositional similarity among multiple genes. Several clusters contained genes that shared 5-6 cis-elements that included ETS and zinc-finger binding sites. cis-Elements AP2 EGRF ETSF MAZF SP1F ZF5F and AREB ETSF MZF1 PAX5 STAT were shared in a thymus-expressed set; AP4R E2FF EBOX ETSF MAZF SP1F ZF5F and CREB E2FF MAZF PCAT SP1F STAT cis-clusters occurred in activated T-cells; CEBP CREB NFKB SORY and GATA NKXH OCTI RBIT occurred in stimulated lymph nodes.Conclusion: This study demonstrates a series of analytic approaches that have allowed the implication of genes and regulatory elements that participate in the differentiation, maintenance, and function of the immune system. Polymorphism or mutation of these could adversely impact immune system functions.