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首页> 外文期刊>Molecular and Cellular Biology >Distinct Transcriptional Pathways Regulate Basal and Activated Major Histocompatibility Complex Class I Expression
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Distinct Transcriptional Pathways Regulate Basal and Activated Major Histocompatibility Complex Class I Expression

机译：不同的转录途径调节基础和激活的主要组织相容性复合体I类表达。

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Transcription of major histocompatibility complex (MHC) class I genes is regulated by both tissue-specific (basal) and hormone/cytokine (activated) mechanisms. Although promoter-proximal regulatory elements have been characterized extensively, the role of the core promoter in mediating regulation has been largely undefined. We report here that the class I core promoter consists of distinct elements that are differentially utilized in basal and activated transcription pathways. These pathways recruit distinct transcription factor complexes to the core promoter elements and target distinct transcription initiation sites. Class I transcription initiates at four major sites within the core promoter and is clustered in two distinct regions: “upstream” (?14 and ?18) and “downstream” (+12 and +1). Basal transcription initiates predominantly from the upstream start site region and is completely dependent upon the general transcription factor TAF1 (TAFII250). Activated transcription initiates predominantly from the downstream region and is TAF1 (TAFII250) independent. USF1 augments transcription initiating through the upstream start sites and is dependent on TAF1 (TAFII250), a finding consistent with its role in regulating basal class I transcription. In contrast, transcription activated by the interferon mediator CIITA is independent of TAF1 (TAFII250) and focuses initiation on the downstream start sites. Thus, basal and activated transcriptions of an MHC class I gene target distinct core promoter domains, nucleate distinct transcription initiation complexes and initiate at distinct sites within the promoter. We propose that transcription initiation at the core promoter is a dynamic process in which the mechanisms of core promoter function differ depending on the cellular environment.
机译：主要组织相容性复合体（MHC）I类基因的转录受组织特异性（基础）和激素/细胞因子（激活）机制的调节。尽管启动子近端调节元件已被广泛表征，但核心启动子在介导调节中的作用尚未明确。我们在这里报告说，I类核心启动子由在基础和激活的转录途径中差异利用的独特元素组成。这些途径将不同的转录因子复合物募集到核心启动子元件并靶向不同的转录起始位点。 I类转录起始于核心启动子内的四个主要位点，并聚集在两个不同的区域：“上游”（？14和？18）和“下游”（+12和+1）。基础转录主要从上游起始位点区域开始，并且完全依赖于一般转录因子TAF1（TAF II 250）。激活的转录主要从下游区域开始，并且独立于TAF1（TAF II 250）。 USF1增强了通过上游起始位点的转录起始，并且依赖于TAF1（TAF II 250），这一发现与其在调节基础I类转录中的作用一致。相反，干扰素介体CIITA激活的转录独立于TAF1（TAF II 250），并且将起始集中在下游起始位点上。因此，MHC I类基因的基础和活化转录靶向不同的核心启动子结构域，成核不同的转录起始复合物并在启动子内的不同位点起始。我们建议在核心启动子的转录起始是一个动态过程，其中核心启动子功能的机制取决于细胞环境而不同。

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