Epigenetic analysis of the critical region I for premature ovarian failure: demonstration of a highly heterochromatic domain on the long arm of the mammalian X chromosome
Epigenetic analysis of the critical region I for premature ovarian failure: demonstration of a highly heterochromatic domain on the long arm of the mammalian X chromosome
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DOI：
10.1136/jmg.2007.056093
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发表时间：
2009-09-01
影响因子：
4
通讯作者：
Toniolo, D.
中科院分区：
文献类型：
--
作者：
Rizzolio, F.;Pramparo, T.;Toniolo, D.
背景：X 染色体重排定义了卵巢早衰 (POF) 的关键区域，该区域在 Xq 中延伸 > 15 Mb。先前已表明该区域可分为两个功能不同的部分，并表明平衡易位中断其近端部分关键区域 1 (CR1)，可能通过下调易位至 X 染色体的卵巢表达常染色体基因而导致 POF。 结果和结论：本研究报告，这种位置效应确实可以通过对 POF 患者体细胞断点区域的分析以及发现 CR1 具有高度异染色质组织的发现来证明，这与 POF 患者的体细胞非常不同。参与重排的常染色体常染色体区域。 POF CR1 的染色质组织可能是 POF 患者中观察到的表观遗传修饰的原因。 CR1 的特征及其在卵母细胞中的下调可以很好地解释其在 POF 中的作用以及涉及 Xq 的染色体重排中 POF 表型的频率。这项研究还证明了 X 染色体长臂的一个大的进化保守结构域，很大程度上对应于 CR1，可能在卵母细胞成熟或 X 染色体失活中具有结构或功能作用。
Background: X chromosome rearrangements defined a critical region for premature ovarian failure (POF) that extended for > 15 Mb in Xq. It has been shown previously that the region could be divided into two functionally distinct portions and suggested that balanced translocations interrupting its proximal part, critical region 1 (CR1), could be responsible for POF through down-regulation of ovary expressed autosomal genes translocated to the X chromosome.Results and conclusion: This study reports that such position effect can indeed be demonstrated by analysis of breakpoint regions in somatic cells of POF patients and by the finding that CR1 has a highly heterochromatic organisation, very different from that of the euchromatic autosomal regions involved in the rearrangements. The chromatin organisation of the POF CR1 is likely to be responsible for the epigenetic modifications observed in POF patients. The characteristics of CR1 and its down-regulation in oocytes may very well explain its role in POF and the frequency of the POF phenotype in chromosomal rearrangements involving Xq. This study also demonstrates a large and evolutionary conserved domain of the long arm of the X chromosome, largely corresponding to CR1, that may have structural or functional roles, in oocyte maturation or in X chromosome inactivation.