Chattopadhyay Samit, Pavithra Lakshminarasimhan
National Center for Cell Science, Pune University Campus, Ganeshkhind, Pune 411007, India.
Subcell Biochem. 2007;41:213-30.
The DNA in eukaryotic genome is compartmentalized into various domains by a series of loops tethered onto the base of nuclear matrix. Scaffold/Matrix attachment regions (S/MAR) punctuate these attachment sites and govern the nuclear architecture by establishing chromatin boundaries. In this context, specific proteins that interact with and bind to MAR sequences called MAR binding proteins (MARBPs), are of paramount importance, as these sequences spool the proteins that regulate transcription, replication, repair and recombination. Recent evidences also suggest a role for these cis-acting elements in viral integration, replication and transcription, thereby affecting host immune system. Owing to the complex nature of these nucleotide sequences, less is known about the MARBPs that bind to and bring about diverse effects on chromatin architecture and gene function. Several MARBPs have been identified and characterized so far and the list is growing. The fact that most the MARBPs exist in a co-repressor/co-activator complex and bring about gene regulation makes them quintessential for cellular processes. This participation in gene regulation means that any perturbation in the regulation and levels of MARBPs could lead to disease conditions, particularly those caused by abnormal cell proliferation, like cancer. In the present chapter, we discuss the role of MARs and MARBPs in eukaryotic gene regulation, recombination, transcription and viral integration by altering the local chromatin structure and their dysregulation in disease manifestation
真核生物基因组中的DNA通过一系列与核基质基部相连的环被分隔成不同的结构域。支架/基质附着区域（S/MAR）贯穿这些附着位点，并通过建立染色质边界来控制核结构。在这种情况下，与MAR序列相互作用并结合的特定蛋白质，即MAR结合蛋白（MARBP），至关重要，因为这些序列缠绕着调节转录、复制、修复和重组的蛋白质。最近的证据还表明，这些顺式作用元件在病毒整合、复制和转录中发挥作用，从而影响宿主免疫系统。由于这些核苷酸序列的复杂性，对于与染色质结构和基因功能结合并产生多种影响的MARBP了解较少。到目前为止，已经鉴定并表征了几种MARBP，而且这个名单还在不断增加。大多数MARBP存在于共抑制因子/共激活因子复合物中并实现基因调控，这一事实使它们成为细胞过程的关键因素。这种对基因调控的参与意味着MARBP调控和水平的任何扰动都可能导致疾病状态，特别是那些由异常细胞增殖引起的疾病，如癌症。在本章中，我们将讨论MAR和MARBP通过改变局部染色质结构在真核生物基因调控、重组、转录和病毒整合中的作用，以及它们在疾病表现中的失调情况
