Regulation of the NF-κB-Mediated Transcription of Inflammatory Genes.
Regulation of the NF-κB-Mediated Transcription of Inflammatory Genes.
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DOI：
10.3389/fimmu.2014.00071
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发表时间：
2014
影响因子：
7.3
通讯作者：
Ghosh S
中科院分区：
文献类型：
--
作者：
Bhatt D;Ghosh S
转录因子NF - κB家族在免疫应答过程中炎症基因的诱导表达中起核心作用，对这些基因的适当调控是维持免疫内稳态的关键因素。刺激应答性NF - κB位点的染色质环境是转录因子结合的主要决定因素，而染色质状态的动态改变以促进转录因子结合是一个关键的调控机制。反过来，NF - κB能够通过多种机制影响染色质状态，包括招募染色质修饰辅激活因子复合物如p300，竞争性去除负性染色质修饰，以及招募通用转录机制的组分。通常，与这些辅激活因子的选择性相互作用取决于NF - κB亚基的特定翻译后修饰。最后，不同免疫细胞类型中诱导性NF - κB活性的机制似乎在很大程度上是保守的。细胞特异性NF - κB介导的转录程序的多样性是在细胞分化过程中由谱系决定转录因子在染色质水平上建立的。这些因子产生并维持一种对NF - κB可及的细胞特异性染色质景观，从而将诱导性转录反应限制在适合细胞的输出。
The NF-κB family of transcription factors plays a central role in the inducible expression of inflammatory genes during the immune response, and the proper regulation of these genes is a critical factor in the maintenance of immune homeostasis. The chromatin environment at stimulus-responsive NF-κB sites is a major determinant in transcription factor binding, and dynamic alteration of the chromatin state to facilitate transcription factor binding is a key regulatory mechanism. NF-κB is in turn able to influence the chromatin state through a variety of mechanisms, including the recruitment of chromatin modifying co-activator complexes such as p300, the competitive eviction of negative chromatin modifications, and the recruitment of components of the general transcriptional machinery. Frequently, the selective interaction with these co-activators is dependent on specific post-translational modification of NF-κB subunits. Finally, the mechanisms of inducible NF-κB activity in different immune cell types seem to be largely conserved. The diversity of cell-specific NF-κB-mediated transcriptional programs is established at the chromatin level during cell differentiation by lineage-defining transcription factors. These factors generate and maintain a cell-specific chromatin landscape that is accessible to NF-κB, thus restricting the inducible transcriptional response to a cell-appropriate output.