Boulikas T
Institute of Molecular Medical Sciences, Palo Alto, California 94306.
J Cell Biochem. 1994 Aug;55(4):513-29. doi: 10.1002/jcb.240550411.
Nuclear matrix is a nuclear protein-DNA superstructure believed to be the exclusive site of DNA replication, transcription, repair, and recombination. The attachment regions of chromatin loops to the nuclear matrix, called MARs, nest origins of replication, have transcriptional enhancer activity, and via their interaction with protein transcription factors may govern gene switch during development and tissue-specific gene expression. In this study the 967 bp MAR of the chicken alpha-globin gene is analyzed for the presence of hexanucleotides from a number (83 in total) of vertebrate protein transcription factors and core origins of replication. A total number of 760 hexanucleotides from factor sites or origins of replication were used for this search. We found that: (1) The occurrence of protein transcription factor binding sites overall on the MAR fragment as well as on the enhancer and promoter regions of other genes is only about 1.2-1.5 times higher than in random DNA, something consistent for all MAR and enhancer sequences examined. However, a high concentration (up to 2.7 times over random sequences) of hexanucleotide factor sites is observed on small stretches of the alpha-globin gene MAR. (2) Some regulatory protein binding sites are underrepresented whereas others are overrepresented, giving to an MAR a particular transcription factor flavor. (3) The DNA curvature map of the MAR sequence and the potential sites of positioned nucleosomes suggest the sites where a competition between core histone octamers and protein transcription factors for DNA might be found. This approach might provide a novel technique to diagnose for the regulatory or nonregulatory function of a stretch of DNA. Furthermore, MARs are proposed to constitute important regulatory elements of genes in addition to enhancers, promoters, silencers, locus control regions, and origins of replication. Additional parameters such as interaction of a transcription factor with other transcription factors fixed at vicinal sites, DNA methylation, intrinsic DNA curvature torsional strain, and nucleosome positioning might also determine the high-affinity binding of a transcription factor to its functional sites and its exclusion from or low affinity binding to other nonregulatory regions.
核基质是一种核蛋白 - DNA 超结构，被认为是 DNA 复制、转录、修复和重组的唯一位点。染色质环与核基质的附着区域，称为 MARs，包含复制起点，具有转录增强子活性，并且通过它们与蛋白质转录因子的相互作用，可能在发育过程中控制基因开关以及组织特异性基因表达。在本研究中，对鸡α - 珠蛋白基因的 967 bp MAR 进行分析，以寻找来自多种（总共 83 种）脊椎动物蛋白质转录因子和复制核心起点的六核苷酸。总共 760 个来自因子位点或复制起点的六核苷酸用于此项搜索。我们发现：（1）MAR 片段以及其他基因的增强子和启动子区域上蛋白质转录因子结合位点的总体出现频率仅比随机 DNA 高约 1.2 - 1.5 倍，这与所有检测的 MAR 和增强子序列一致。然而，在α - 珠蛋白基因 MAR 的小片段上观察到六核苷酸因子位点高度集中（比随机序列高至 2.7 倍）。（2）一些调节蛋白结合位点代表性不足，而其他位点则代表性过高，赋予 MAR 一种特定的转录因子特征。（3）MAR 序列的 DNA 曲率图谱和定位核小体的潜在位点表明，可能存在核心组蛋白八聚体与蛋白质转录因子对 DNA 竞争的位点。这种方法可能提供一种新技术来诊断一段 DNA 的调节或非调节功能。此外，除了增强子、启动子、沉默子、基因座控制区和复制起点外，MARs 被认为是基因的重要调节元件。其他参数，如转录因子与固定在相邻位点的其他转录因子之间的相互作用、DNA 甲基化、内在 DNA 曲率扭转应变和核小体定位，也可能决定转录因子与其功能位点的高亲和力结合以及其与其他非调节区域的排斥或低亲和力结合。
