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首页> 外文期刊>Molecular and Cellular Biology >Coordination of Cell Signaling, Chromatin Remodeling, Histone Modifications, and Regulator Recruitment in Human Matrix Metalloproteinase 9 Gene Transcription
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Coordination of Cell Signaling, Chromatin Remodeling, Histone Modifications, and Regulator Recruitment in Human Matrix Metalloproteinase 9 Gene Transcription

机译：细胞信号，染色质重塑，组蛋白修饰和人类基质金属蛋白酶9基因转录中的调节剂招募的协调。

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摘要

Transcriptional activation of eukaryotic genes depends on the precise and ordered recruitment of activators, chromatin modifiers/remodelers, coactivators, and general transcription factors to the promoters of target genes. Using the human matrix metalloproteinase 9 (MMP-9) gene as a model system, we investigated the sequential assembly and dynamic formation of transcription complexes on a human promoter under the influence of mitogen signaling. We find that, coincident with activation of the MMP-9 gene, activators, chromatin remodeling complexes, and coactivators are recruited to the preassembled MMP-9 promoter in a stepwise and coordinated order, which is dependent on activation of MEK-1/extracellular signal-regulated kinase and NF-κB signaling pathways. Conversely, corepressor complexes are released from the MMP-9 promoter after transcriptional activation. Histone modifications shift from repressive to permissive modifications concurrent with activation of the MMP-9 gene. Chromatin remodeling induced by Brg-1 is required for MMP-9 gene transcription, which is concomitant with initiation of transcription. Therefore, coordination of cell signaling, chromatin remodeling, histone modifications, and stepwise recruitment of transcription regulators is critical to precisely regulate MMP-9 gene transcription in a temporally and spatially dependent manner. Given the important role of MMP-9 in both normal development and pathological conditions, understanding MMP-9 gene regulation is of great relevance.
机译：真核基因的转录激活取决于目标基因启动子的激活剂，染色质修饰剂/重塑剂，共激活剂和一般转录因子的精确有序募集。使用人类基质金属蛋白酶9（MMP-9）基因作为模型系统，我们调查了有丝分裂原信号转导下人类启动子上转录复合物的顺序组装和动态形成。我们发现，与MMP-9基因的激活相一致，激活剂，染色质重塑复合体和共激活剂以逐步和协调的顺序募集到预装配的MMP-9启动子，这取决于MEK-1 /细胞外信号的激活调节激酶和NF-κB信号通路。相反，转录激活后，MMP-9启动子释放了corepressor复合物。组蛋白修饰在激活MMP-9基因的同时从抑制性修饰转变为允许性修饰。 Brg-1诱导的染色质重塑是MMP-9基因转录所必需的，这与转录的启动同时进行。因此，细胞信号传导，染色质重塑，组蛋白修饰和转录调节剂的逐步募集的协调对于以时间和空间依赖性方式精确调节MMP-9基因的转录至关重要。鉴于MMP-9在正常发育和病理状况中都具有重要作用，因此了解MMP-9基因调控具有重要意义。

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