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SAF-Box, a Conserved Protein Domain That Specifically Recognizes Scaffold Attachment Region DNA

机译:SAF-Box,一种保守的蛋白质结构域,专门识别支架附着区DNA

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SARs (scaffold attachment regions) are candidate DNA elements for partitioning eukaryotic genomes into independent chromatin loops by attaching DNA to proteins of a nuclear scaffold or matrix. The interaction of SARs with the nuclear scaffold is evolutionarily conserved and appears to be due to specific DNA binding proteins that recognize SARs by a mechanism not yet understood. We describe a novel, evolutionarily conserved protein domain that specifically binds to SARs but is not related to SAR binding motifs of other proteins. This domain was first identified in human scaffold attachment factor A (SAF-A) and was thus designated SAF-Box. The SAF-Box is present in many different proteins ranging from yeast to human in origin and appears to be structurally related to a homeodomain. We show here that SAF-Boxes from four different origins, as well as a synthetic SAF-Box peptide, bind to natural and artificial SARs with high specificity. Specific SAR binding of the novel domain is achieved by an unusual mass binding mode, is sensitive to distamycin but not to chromomycin, and displays a clear preference for long DNA fragments. This is the first characterization of a specific SAR binding domain that is conserved throughout evolution and has DNA binding properties that closely resemble that of the unfractionated nuclear scaffold.
机译:SAR(支架附着区)是通过将DNA附着在核支架或基质蛋白上而将真核基因组划分为独立染色质环的候选DNA元件。 SAR与核支架的相互作用在进化上是保守的,并且似乎归因于通过尚不了解的机制识别SAR的特定DNA结合蛋白。我们描述了一种新型的,进化上保守的蛋白质结构域,该结构域特异性结合SAR,但与其他蛋白质的SAR结合基序无关。该结构域首先在人支架附着因子A(SAF-A)中鉴定,因此被命名为SAF-Box。 SAF-Box存在于从酵母到人的许多不同蛋白质中,起源于人类,并且似乎与同源结构域在结构上相关。我们在这里显示来自四个不同来源的SAF-Boxs以及合成的SAF-Box肽以高特异性结合天然和人工SAR。新结构域的特异性SAR结合是通过不寻常的质量结合模式实现的,它对双霉素敏感但对染色体霉素不敏感,并且对长DNA片段表现出明显的偏好。这是特定SAR结合结构域的第一个特征,该结构在整个进化过程中都是保守的,其DNA结合特性与未分级的核支架非常相似。

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