How the proteome packages the genome for cardiovascular development.
How the proteome packages the genome for cardiovascular development.
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DOI：
10.1002/pmic.201400131
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发表时间：
2014-10
期刊：
影响因子：
3.4
通讯作者：
Vondriska, Thomas M.
中科院分区：
文献类型：
--
作者：
Karbassi, Elaheh;Vondriska, Thomas M.
先天性心脏缺陷的破坏性影响使得脊椎动物心脏和血管发育的机制成为一个活跃的研究领域。由于心肌细胞死亡是获得性心血管疾病的共同特征，而成人心脏不能再生，因此有必要了解发育中的心脏和血管系统的特征（它们更具可塑性）是否可以用于疾病的治疗。我们知道，转录因子的核心网络控制着心血管谱系的承诺，最近使用遗传功能丧失方法和无偏倚基因组研究的研究揭示了各种染色质调节事件的作用。我们认为染色质结构本身是影响发育连续体转录组复杂性的一个因果特征，本文的目的是强调组学技术有可能揭示发育中表型可塑性新原理的领域。我们回顾了染色质结构调节的主要机制，强调了它们控制心血管分化的已知作用。我们讨论了在细胞核基因组学和蛋白质组学研究的基础上已经确定的调控机制，并确定了当前对染色质结构和心血管表型的综合理解的挑战。
The devastating impact of congenital heart defects has made mechanisms of vertebrate heart and vascular development an active area of study. Because myocyte death is a common feature of acquired cardiovascular diseases and the adult heart does not regenerate, the need exists to understand whether features of the developing heart and vasculature—which are more plastic—can be exploited therapeutically in the disease setting. We know that a core network of transcription factors governs commitment to the cardiovascular lineage, and recent studies using genetic loss-of-function approaches and unbiased genomic studies have revealed the role for various chromatin modulatory events. We reason that chromatin structure itself is a causal feature that influences transcriptome complexity along a developmental continuum, and the purpose of this article is to highlight the areas in which ‘omics technologies have the potential to reveal new principles of phenotypic plasticity in development. We review the major mechanisms of chromatin structural regulation, highlighting what is known about their actions to control cardiovascular differentiation. We discuss emergent mechanisms of regulation that have been identified on the basis of genomic and proteomic studies of cardiac nuclei and identify current challenges to an integrated understanding of chromatin structure and cardiovascular phenotype.
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