Programming smooth muscle plasticity with chromatin dynamics
Programming smooth muscle plasticity with chromatin dynamics
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DOI：
10.1161/01.res.0000266448.30370.a0
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发表时间：
2007-05-25
影响因子：
20.1
通讯作者：
Owens, Gary K.
中科院分区：
文献类型：
--
作者：
McDonald, Oliver G.;Owens, Gary K.
平滑肌细胞（SMC）具有显著的表型可塑性，可以快速适应波动的环境线索。例如，血管SMC在响应于血管损伤的新生内膜形成期间或在动脉粥样硬化斑块内经历其表型的深刻变化。最近的研究表明，血清反应因子（SRF）及其众多辅助辅因子与SMC基因启动子染色质内的CArG盒DNA序列的相互作用是影响SMC在发育和疾病中分化的整合信号的联系。在发育过程中，SMC限制的组蛋白翻译后修饰集在SMC基因的CArG盒染色质内获得。这些修饰反过来控制SRF的染色质结合特性。组蛋白修饰似乎编码SMC特异性表观遗传程序，该程序被细胞外线索用于通过调节SRF及其伴侣与染色质模板的结合来影响SMC分化。因此，SMC分化是动态调节SRF辅助辅因子之间的相互作用，SRF-CArG相互作用，和潜在的组蛋白修饰程序。因此，SMC谱系的固有可塑性提供了独特的一瞥，了解细胞分化如何在变化的微环境中在染色质水平上动态控制。进一步阐明染色质如何调节SMC分化无疑将产生有价值的见解正常发育过程和几种血管疾病的发病机制，显示有害的SMC表型行为。
Smooth muscle cells (SMCs) possess remarkable phenotypic plasticity that allows rapid adaptation to fluctuating environmental cues. For example, vascular SMCs undergo profound changes in their phenotype during neointimal formation in response to vessel injury or within atherosclerotic plaques. Recent studies have shown that interaction of serum response factor (SRF) and its numerous accessory cofactors with CArG box DNA sequences within promoter chromatin of SMC genes is a nexus for integrating signals that influence SMC differentiation in development and disease. During development, SMC-restricted sets of posttranslational histone modifications are acquired within the CArG box chromatin of SMC genes. These modifications in turn control the chromatin-binding properties of SRF. The histone modifications appear to encode a SMC-specific epigenetic program that is used by extracellular cues to influence SMC differentiation, by regulating binding of SRF and its partners to the chromatin template. Thus, SMC differentiation is dynamically regulated by the interplay between SRF accessory cofactors, the SRF-CArG interaction, and the underlying histone modification program. As such, the inherent plasticity of the SMC lineage offers unique glimpses into how cellular differentiation is dynamically controlled at the level of chromatin within the context of changing microenvironments. Further elucidation of how chromatin regulates SMC differentiation will undoubtedly yield valuable insights into both normal developmental processes and the pathogenesis of several vascular diseases that display detrimental SMC phenotypic behavior.