Attachment to the nuclear matrix mediates specific alterations in chromatin structure.
Attachment to the nuclear matrix mediates specific alterations in chromatin structure.
复制标题
与核基质的附着介导染色质结构的特定改变。
DOI：
10.1073/pnas.95.25.14757
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发表时间：
1998
影响因子：
11.1
通讯作者：
Hamlin,JL
中科院分区：
文献类型：
--
作者：
Pemov,A;Bavykin,S;Hamlin,JL
真核染色体中的 DNA 被组织成一系列环，这些环的碱基永久附着在核支架或基质上，序列称为支架附着区或基质附着区。目前，尚不清楚附着在核基质上对复制起点或基因启动子区域等重要调控区域的染色质结构有何影响。在本研究中，我们研究了甲氨蝶呤抗性中国仓鼠卵巢细胞系 CHOC 400 的扩增二氢叶酸还原酶结构域中复制起始区的染色质结构的细胞周期依赖性变化，该结构域已被充分表征。复制可以在分散在该结构域中 55 KB 基因间区域的多个潜在位点中的任何一个位点启动，其中两个子区域（termedori-βandori-γ）在某种程度上是优选的。我们在此表明，当细胞跨越 G1/S 边界时，theori-βandori-γ 区域中的染色质会经历微球菌核酸酶超敏性的显着改变，但仅限于固定在核基质上的那些扩增子副本。相反，二氢叶酸还原酶基因启动子中染色质的精细结构不会随着基质附着或细胞周期位置而发生可检测到的变化。我们认为 DNA 与核基质的附着在调节染色质结构中发挥着重要作用，这可能促进复制起点的活性。
The DNA in eukaryotic chromosomes is organized into a series of loops that are permanently attached at their bases to the nuclear scaffold or matrix at sequences known as scaffold-attachment or matrix-attachment regions. At present, it is not clear what effect affixation to the nuclear matrix has on chromatin architecture in important regulatory regions such as origins of replication or the promoter regions of genes. In the present study, we have investigated cell-cycle-dependent changes in the chromatin structure of a well characterized replication initiation zone in the amplified dihydrofolate reductase domain of the methotrexate-resistant Chinese hamster ovary cell line CHOC 400. Replication can initiate at any of multiple potential sites scattered throughout the 55-kilobase intergenic region in this domain, with two subregions (termedori-βandori-γ) being somewhat preferred. We show here that the chromatin in theori-βandori-γregions undergoes dramatic alterations in micrococcal nuclease hypersensitivity as cells cross the G1/S boundary, but only in those copies of the amplicon that are affixed to the nuclear matrix. In contrast, the fine structure of chromatin in the promoter of the dihydrofolate reductase gene does not change detectably as a function of matrix attachment or cell-cycle position. We suggest that attachment of DNA to the nuclear matrix plays an important role in modulating chromatin architecture, and this could facilitate the activity of origins of replication.