LINE retrotransposon RNA is an essential structural and functional epigenetic component of a core neocentromeric chromatin.
LINE retrotransposon RNA is an essential structural and functional epigenetic component of a core neocentromeric chromatin.
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DOI：
10.1371/journal.pgen.1000354
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发表时间：
2009-01
期刊：
影响因子：
4.5
通讯作者：
Wong, Lee H.
中科院分区：
文献类型：
--
作者：
Chueh, Anderly C.;Northrop, Emma L.;Brettingham-Moore, Kate H.;Choo, K. H. Andy;Wong, Lee H.
我们以前已经确定和特点的现象异位人类着丝粒，称为新着丝粒。人类新着丝粒在常染色质染色体位点表观遗传地形成，并且在结构和功能上与正常人类着丝粒相似。最近的研究表明，新着丝粒的形成提供了一个主要的机制，着丝粒重新定位，核型进化和物种形成。使用标记染色体martel（10）含有在正常染色体10 q25区域形成的新着丝粒，我们以前绘制了一个330 kb的CENP-A结合结构域，并描述了在CENP-A结合簇的基础DNA序列中L1反转录转座子的流行率增加。在这里，我们研究了L1反转录转座子在调节新着丝粒活性中的潜在作用。通过测定跨越10 q25新着丝粒染色质的6-Mb区域的一组全长L1（FL-L1）的转录活性，确定了一个FL-L1逆转录转座子，命名为FL-L1 b，位于CENP-A结合簇的中心，具有转录活性。我们证明了FL-L1 b RNA转录物直接掺入CENP-A相关染色质。RNAi介导的FL-L1 b RNA转录物的敲低导致CENP-A结合减少和10 q25新着丝粒的有丝分裂功能受损。这些结果表明，LINE反转录转座子RNA是一个以前未描述的新着丝粒染色质的基本结构和功能的组成部分，反转录转座因子可能作为一个关键的表观遗传决定因素的染色质重塑事件导致新着丝粒的形成。着丝粒是细胞分裂过程中染色体正确分离所必需的染色体结构。正常人的着丝粒由一个171 bp的α-卫星DNA组成，排列成串联和高阶阵列。新着丝粒是在染色体的非着丝粒区域上表观遗传形成的功能齐全的着丝粒，最近的证据表明它们在着丝粒重新定位、核型进化和物种形成中发挥重要作用。新着丝粒含有完全可定义的DNA序列，并提供了一个易于处理的系统，用于着丝粒染色质的分子分析。在这里，作者研究了表观遗传决定因素在调节新着丝粒结构和功能中的作用。他们确定了在新着丝粒结构域内发现的逆转录转座DNA元件是活跃转录的，并且转录的RNA对于新着丝粒的结构和功能完整性是必不可少的。这项研究定义了一个以前未描述的表观遗传决定因素，调节新着丝粒染色质，并提供了深入了解新着丝粒形成和着丝粒重新定位的机制。
We have previously identified and characterized the phenomenon of ectopic human centromeres, known as neocentromeres. Human neocentromeres form epigenetically at euchromatic chromosomal sites and are structurally and functionally similar to normal human centromeres. Recent studies have indicated that neocentromere formation provides a major mechanism for centromere repositioning, karyotype evolution, and speciation. Using a marker chromosome mardel(10) containing a neocentromere formed at the normal chromosomal 10q25 region, we have previously mapped a 330-kb CENP-A–binding domain and described an increased prevalence of L1 retrotransposons in the underlying DNA sequences of the CENP-A–binding clusters. Here, we investigated the potential role of the L1 retrotransposons in the regulation of neocentromere activity. Determination of the transcriptional activity of a panel of full-length L1s (FL-L1s) across a 6-Mb region spanning the 10q25 neocentromere chromatin identified one of the FL-L1 retrotransposons, designated FL-L1b and residing centrally within the CENP-A–binding clusters, to be transcriptionally active. We demonstrated the direct incorporation of the FL-L1b RNA transcripts into the CENP-A–associated chromatin. RNAi-mediated knockdown of the FL-L1b RNA transcripts led to a reduction in CENP-A binding and an impaired mitotic function of the 10q25 neocentromere. These results indicate that LINE retrotransposon RNA is a previously undescribed essential structural and functional component of the neocentromeric chromatin and that retrotransposable elements may serve as a critical epigenetic determinant in the chromatin remodelling events leading to neocentromere formation. The centromere is an essential chromosomal structure for the correct segregation of chromosomes during cell division. Normal human centromeres comprise a 171-bp α-satellite DNA arranged into tandem and higher-order arrays. Neocentromeres are fully functional centromeres that form epigenetically on noncentromeric regions of the chromosomes, with recent evidence indicating an important role they play in centromere repositioning, karyotype evolution, and speciation. Neocentromeres contain fully definable DNA sequences and provide a tractable system for the molecular analysis of the centromere chromatin. Here, the authors investigate the role of epigenetic determinants in the regulation of neocentromere structure and function. They identify that a retrotransposable DNA element found within the neocentromere domain is actively transcribed and that the transcribed RNA is essential for the structural and functional integrity of the neocentromere. This study defines a previously undescribed epigenetic determinant that regulates the neocentromeric chromatin and provides insight into the mechanism of neocentromere formation and centromere repositioning.
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影响因子：
11.4
作者：
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DOI：
10.1073/pnas.0507947103
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2006-03-14
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Sullivan, BA
DOI：
10.1073/pnas.87.18.6990
发表时间：
1990-09-01
影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.0308637101
发表时间：
2004-04-27
影响因子：
11.1
作者：
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通讯作者：
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