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首页> 外文期刊>BMC Veterinary Research >Combinatorial motif analysis of regulatory gene expression in Mafb deficient macrophages
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Combinatorial motif analysis of regulatory gene expression in Mafb deficient macrophages

机译：Mafb缺陷巨噬细胞中调控基因表达的组合基序分析

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BackgroundDeficiency of the transcription factor MafB, which is normally expressed in macrophages, can underlie cellular dysfunction associated with a range of autoimmune diseases and arteriosclerosis. MafB has important roles in cell differentiation and regulation of target gene expression; however, the mechanisms of this regulation and the identities of other transcription factors with which MafB interacts remain uncertain. Bioinformatics methods provide a valuable approach for elucidating the nature of these interactions with transcriptional regulatory elements from a large number of DNA sequences. In particular, identification of patterns of co-occurrence of regulatory cis-elements (motifs) offers a robust approach.ResultsHere, the directional relationships among several functional motifs were evaluated using the Log-linear Graphical Model (LGM) after extraction and search for evolutionarily conserved motifs. This analysis highlighted GATA-1 motifs and 5’AT-rich half Maf recognition elements (MAREs) in promoter regions of 18 genes that were down-regulated in Mafb deficient macrophages. GATA-1 motifs and MafB motifs could regulate expression of these genes in both a negative and positive manner, respectively. The validity of this conclusion was tested with data from a luciferase assay that used a C1qa promoter construct carrying both the GATA-1 motifs and MAREs. GATA-1 was found to inhibit the activity of the C1qa promoter with the GATA-1 motifs and MafB motifs.ConclusionsThese observations suggest that both the GATA-1 motifs and MafB motifs are important for lineage specific expression of C1qa. In addition, these findings show that analysis of combinations of evolutionarily conserved motifs can be successfully used to identify patterns of gene regulation.
机译：背景通常在巨噬细胞中表达的转录因子MafB的缺乏可能是与一系列自身免疫性疾病和动脉硬化相关的细胞功能障碍的基础。 MafB在细胞分化和调控靶基因表达中具有重要作用;但是，这种调控的机制以及与MafB相互作用的其他转录因子的身份仍然不确定。生物信息学方法为阐明这些相互作用与来自大量DNA序列的转录调控元件的本质提供了一种有价值的方法。尤其是鉴定调控性顺式元件（基序）共现的模式提供了一种可靠的方法。保守的图案。这项分析突出显示了在缺乏Mafb的巨噬细胞中被下调的18个基因的启动子区域中的GATA-1基序和富含5'AT的半Maf识别元件（MARE）。 GATA-1主题和MafB主题可以分别以负面和正面的方式调节这些基因的表达。该结论的有效性用萤光素酶测定的数据进行了测试，该数据使用了同时带有GATA-1基序和MARE的C1qa启动子构建体。发现GATA-1抑制具有GATA-1模体和MafB模体的C1qa启动子活性。此外，这些发现表明，进化保守基序组合的分析可成功用于鉴定基因调控模式。

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