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哺乳动物着丝粒蛋白结合的表观遗传控制:DNA甲基化起作用吗?

Epigenetic control of mammalian centromere protein binding: does DNA methylation have a role?

作者信息

Mitchell A R, Jeppesen P, Nicol L, Morrison H, Kipling D

机构信息

MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.

出版信息

J Cell Sci. 1996 Sep;109 ( Pt 9):2199-206. doi: 10.1242/jcs.109.9.2199.

DOI:10.1242/jcs.109.9.2199
PMID:8886971
Abstract

Chromosome 1 of the inbred mouse strain DBA/2 has a polymorphism associated with the minor satellite DNA at its centromere. The more terminal block of satellite DNA sequences on this chromosome acts as the centromere as shown by the binding of CREST ACA serum, anti-CENP-B and anti-CENP-E polyclonal sera. Demethylation of the minor satellite DNA sequences accomplished by growing cells in the presence of the drug 5-aza-2'-deoxycytidine results in a redistribution of the CENP-B protein. This protein now binds to an enlarged area on the more terminal block and in addition it now binds to the more internal block of minor satellite DNA sequences on chromosome 1. The binding of the CENP-E protein does not appear to be affected by demethylation of the minor satellite sequences. We present a model to explain these observations. This model may also indicate the mechanism by which the CENP-B protein recognises specific sites within the arrays of minor satellite DNA on mouse chromosomes.

摘要

近交系小鼠DBA/2的1号染色体在其着丝粒处存在与小卫星DNA相关的多态性。如CREST ACA血清、抗CENP - B和抗CENP - E多克隆血清的结合所示,该染色体上卫星DNA序列的更末端区域起着丝粒的作用。在药物5 - 氮杂 - 2'-脱氧胞苷存在下培养细胞,使小卫星DNA序列去甲基化,导致CENP - B蛋白重新分布。该蛋白现在结合到更末端区域的扩大区域,此外,它现在还结合到1号染色体上小卫星DNA序列的更内部区域。CENP - E蛋白的结合似乎不受小卫星序列去甲基化的影响。我们提出了一个模型来解释这些观察结果。该模型也可能表明CENP - B蛋白识别小鼠染色体上小卫星DNA阵列内特定位点的机制。

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