Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
BMC Genomics. 2011 Jun 27;12:330. doi: 10.1186/1471-2164-12-330.
MicroRNAs (miRNAs) play a fundamental role in the regulation of gene expression by translational repression or target mRNA degradation. Regulatory elements in miRNA promoters are less well studied, but may reveal a link between their expression and a specific cell type.
To explore this link in myeloid cells, miRNA expression profiles were generated from monocytes and dendritic cells (DCs). Differences in miRNA expression among monocytes, DCs and their stimulated progeny were observed. Furthermore, putative promoter regions of miRNAs that are significantly up-regulated in DCs were screened for Transcription Factor Binding Sites (TFBSs) based on TFBS motif matching score, the degree to which those TFBSs are over-represented in the promoters of the up-regulated miRNAs, and the extent of conservation of the TFBSs in mammals.
Analysis of evolutionarily conserved TFBSs in DC promoters revealed preferential clustering of sites within 500 bp upstream of the precursor miRNAs and that many mRNAs of cognate TFs of the conserved TFBSs were indeed expressed in the DCs. Taken together, our data provide evidence that selected miRNAs expressed in DCs have evolutionarily conserved TFBSs relevant to DC biology in their promoters.
微小 RNA（miRNAs）通过翻译抑制或靶 mRNA 降解在基因表达调控中发挥着根本作用。miRNA 启动子中的调控元件研究得较少，但它们可能揭示了它们的表达与特定细胞类型之间的联系。
为了探索髓样细胞中的这种联系，从单核细胞和树突状细胞（DC）中生成了 miRNA 表达谱。观察到单核细胞、DC 及其刺激后代之间 miRNA 表达的差异。此外，根据转录因子结合位点（TFBS）基序匹配分数、TFBS 在上调 miRNA 启动子中过度表达的程度以及 TFBS 在哺乳动物中的保守程度，筛选了在 DC 中显著上调的 miRNA 的推定启动子区域中的 TFBS。
对 DC 启动子中进化上保守的 TFBS 的分析表明，在 miRNA 前体的上游 500bp 内优先聚类位点，并且保守 TFBS 的许多同源 TF 的 mRNAs 实际上在 DC 中表达。总之，我们的数据提供了证据，表明在 DC 中表达的选定 miRNA 在其启动子中具有与 DC 生物学相关的进化上保守的 TFBS。
