Nucleotide sequence of the intron of the germline human kappa immunoglobulin gene connecting the J and C regions reveals a matrix association region (MAR) next to the enhancer.
Nucleotide sequence of the intron of the germline human kappa immunoglobulin gene connecting the J and C regions reveals a matrix association region (MAR) next to the enhancer.
复制标题
连接 J 区和 C 区的种系人 kappa 免疫球蛋白基因内含子的核苷酸序列揭示了增强子旁边的基质关联区 (MAR)。
DOI：
10.1093/nar/20.18.4929
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发表时间：
1992
影响因子：
14.9
通讯作者：
Garrard,WT
中科院分区：
文献类型：
--
作者：
Whitehurst,C;Henney,HR;Max,EE;SchroederJr,HW;Stüber,F;Siminovitch,KA;Garrard,WT
DNA withininterphase nuclei and mitotic chromosomes is believed to be organized into topologically constrained looped domains ranging from 5 to 200 kb in length (reviewed in refs. 1, 2). In vitro DNA binding assays have identified sequences termed MARs ('matrix association regions'), also called SARs ('scaffold attached regions'), that are thought to mediate loop attachment in vivo (3, 4). These sequences are at least 200 bp long, AT-rich (ca. 70%), and often contain topoisomerase II and other AT-rich consensus motifs (1). MARs appear to be evolutionarily conserved, since similar sequences have been identified in DNA derived from human, mouse, hamster, chicken, rabbit, Drosophila and yeast, as well as viral genomes. These elements also appear to have prokaryotic counterparts (1). Particularly intriguing is the observation that the x immunogobulin genes of the mouse and rabbit have MARs adjacent to their intronic transcriptional enhancer elements (3, 5). Stable integration experiments with constructs lacking the mouse MAR and natural mutations of the corresponding region in the rabbit gene reveal that the MARs are neccessary for maximal gene expression (6, 7). The mouse immunoglobulin heavy chain gene enhancer also is flanked by MARs (8), and a MAR has been identified within the chicken X immunogobulin constant region locus (9). Here we address the qutestion of whether a MAR resides within the human x immunoglobulin gene in a position similar to that of the mouse and rabbit counterparts. Although portions of the human x gene locus have been sequenced (10-14), the relevant region predicted to contain a MAR remained to be characterized (Figure 1). We therefore resequenced segments of the locus including an additional previously unreported 1.9 kb and thereby generated a contiguous updated sequence spanning 5364 nucleotides (Accession no. X67858 in the EMBL Database). Based on the AT-content, frequency of ATATTT, and topoisomerase II consensus sequences (3), we conclude that a MAR resides within the human x gene just upstream of the enhancer (Figure 1). Dot matrix analysis further confirms this assignment since the humanMAR shares sequence similarity with its mouse and rabbit counterparts (Figure 2).
