Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require CCAAT/enhancer-binding protein β-dependent recruitment of SWI/SNF activity
Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require CCAAT/enhancer-binding protein β-dependent recruitment of SWI/SNF activity
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DOI：
10.1074/jbc.m511640200
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发表时间：
2006-08-11
影响因子：
4.8
通讯作者：
Montecino, Martin
中科院分区：
文献类型：
--
作者：
Villagra, Alejandro;Cruzat, Fernando;Montecino, Martin
骨钙素（OC）基因的组织特异性激活与启动子区染色质结构的变化有关。两个核酸酶超敏位点跨越控制基底组织特异性和维生素D-3增强的OC基因转录的关键调控元件。为了了解OC基因染色质重塑的分子机制，我们研究了SWI/SNF活性的要求。我们诱导表达了ATP酶缺陷的BRG 1催化亚基，形成无活性的SWI/SNF复合物，结合到OC启动子。这种相互作用导致基础和维生素D-3增强的OC基因转录的抑制和核酸酶超敏性的显着降低。我们发现SWI/SNF通过转录因子CCAAT/增强子结合蛋白β被募集到OC启动子，该转录因子与Runx2一起形成稳定的复合物，以促进RNA聚合酶II结合和OC基因转录的激活。总之，我们的研究结果表明，SWI/SNF复合物是促进成骨细胞组织特异性转录的染色质重塑事件的关键调节因子。
Tissue-specific activation of the osteocalcin (OC) gene is associated with changes in chromatin structure at the promoter region. Two nuclease-hypersensitive sites span the key regulatory elements that control basal tissue-specific and vitamin D-3-enhanced OC gene transcription. To gain understanding of the molecular mechanisms involved in chromatin remodeling of the OC gene, we have examined the requirement for SWI/SNF activity. We inducibly expressed an ATPase-defective BRG1 catalytic subunit that forms inactive SWI/SNF complexes that bind to the OC promoter. This interaction results in inhibition of both basal and vitamin D-3-enhanced OC gene transcription and a marked decrease in nuclease hypersensitivity. We find that SWI/SNF is recruited to the OC promoter via the transcription factor CCAAT/enhancer-binding protein beta, which together with Runx2 forms a stable complex to facilitate RNA polymerase II binding and activation of OC gene transcription. Together, our results indicate that the SWI/SNF complex is a key regulator of the chromatin-remodeling events that promote tissue-specific transcription in osteoblasts.