STRUCTURE OF A NUCLEASE-SENSITIVE REGION INSIDE THE IMMUNOGLOBIN KAPPA-GENE - EVIDENCE FOR A ROLE IN GENE-REGULATION

STRUCTURE OF A NUCLEASE-SENSITIVE REGION INSIDE THE IMMUNOGLOBIN KAPPA-GENE - EVIDENCE FOR A ROLE IN GENE-REGULATION
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DOI:
10.1093/nar/11.14.4775
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发表时间:
1983-01-01
影响因子:
14.9
通讯作者:
GRANNER, DK
GRANNER, DK
中科院分区:
生物学2区
文献类型:
--
作者:
PARSLOW, TG;GRANNER, DK

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活性免疫球蛋白kappa基因内的一个离散染色质区域优先被核解酶切割。该区域由200-250个核苷酸组成,位于该基因的大内含子内,恒定区编码序列上游约600个核苷酸。该区域的局部染色质结构与组织特异性kappa基因的表达相关:在小鼠脑和肝细胞核的非活性kappa基因中,它抵抗核溶解消化,但对脱氧核糖核酸酶I或产生kappa的细胞染色质中的各种限制性内切酶的切割变得唯一敏感。核酸酶的敏感性在重排和未重排的kappa等位基因中都存在,并且可以在没有kappa转录的情况下保持不变。超敏区的核苷酸序列在进化过程中被选择性地保守,它包括一个7bp的反向重复序列和一个与某些真核病毒转录增强元件同源的短片段。发生在该位点的分子事件可能通过影响上游几千碱基的启动子序列的活性,在kappa基因的表达调控中发挥作用。
A discrete chromatin region inside the active immunoglobulin kappa gene is preferentially accessible to cleavage by nucleolytic enzymes. This region comprises 200–250 bp of DNA, and is situated within the large intron of the gene, approximately 600 bp upstream from the constant region coding sequence. The local chromatin structure of this region correlates with tissue-specific kappa gene expression: it is resistant to nucleolytic digestion in the inactive kappa genes of murine brain and liver nuclei, but becomes uniquely sensitive to cleavage by deoxyribonuclease I or by a variety of restriction endonucleases in the chromatin of kappa-producing cells. Nuclease sensitivity at this site occurs in both rearranged and unrearranged kappa alleles, and can be maintained in the absence of ongoing kappa transcription. The nucleotide sequence of the hypersensitive region has been selectively conserved in evolution, and includes both a 7 bp inverted repeat sequence and a short segment homologous to the transcriptional enhancer elements of certain eukaryotic viruses. Molecular events occuring at this locus may play a role in the regulation of kappa gene expression, perhaps by influencing the activity of promoter sequences several kilobases upstream.