Permissive transcriptional activity at the centromere through pockets of DNA hypomethylation.
Permissive transcriptional activity at the centromere through pockets of DNA hypomethylation.
复制标题
通过DNA低甲基化的口袋在丝粒处的允许转录活性。
DOI：
10.1371/journal.pgen.0020017
复制
发表时间：
2006-02
期刊：
影响因子：
4.5
通讯作者：
Choo, K. H. Andy
中科院分区：
文献类型：
--
作者：
Wong, Nicholas C.;Wong, Lee H.;Quach, Julie M.;Canham, Paul;Craig, Jeffrey M.;Song, Jenny Z.;Clark, Susan J.;Choo, K. H. Andy
DNA甲基化是转录沉默的标志，但着丝粒转录已有报道。为了解决这一明显的悖论，我们采用了完全序列定义的异位人类着丝粒(或新着丝粒)来研究DNA甲基化和转录之间的关系。我们使用亚硫酸氢钠聚合酶链式反应和测序来确定2,041个CpG二核苷酸的甲基化状态，这些二核苷酸分布在包含新着丝粒的6.76-MBP染色体区域。这些CpG二核苷酸与常规和非常规CpG岛相关。我们发现新着丝粒DNA在非常规的CpG岛上发生了全面的超甲基化，我们将其命名为CpG胰岛和CpG孤儿。观察到的高甲基化与推测新着丝粒存在转录沉默的染色质状态是一致的。在这个新着丝粒染色质中，活跃转录的特定位置和着丝粒染色质边界由DNA低甲基化定义。据我们所知，我们的数据首次证明了DNA甲基化与哺乳动物着丝粒形成之间的相关性，并且通过选择性地对一些序列进行低甲基化，在着丝粒上允许转录和“染色质边界活动”，而不会损害着丝粒的整体沉默染色质状态和功能。着丝粒是一种染色体结构，在细胞分裂过程中对染色体的正确划分至关重要。最近在许多不同物种中的研究表明，着丝粒内的转录是允许的，但着丝粒的转录调控模式尚不清楚。DNA甲基化是基因组转录调控的一种典型机制。在这里，作者调查了DNA甲基化和功能人类着丝粒转录活性之间的关系。他们证明着丝粒上的DNA甲基化水平很高，但识别出甲基化区域内的一些非甲基化的DNA序列。这些口袋对应于转录位置和/或分隔主要着丝粒染色质亚域的边界。这项研究显示了着丝粒的复杂性，因为它使用DNA甲基化来维持紧密的染色质结构，并允许转录发生。
DNA methylation is a hallmark of transcriptional silencing, yet transcription has been reported at the centromere. To address this apparent paradox, we employed a fully sequence-defined ectopic human centromere (or neocentromere) to investigate the relationship between DNA methylation and transcription. We used sodium bisulfite PCR and sequencing to determine the methylation status of 2,041 CpG dinucleotides distributed across a 6.76-Mbp chromosomal region containing a neocentromere. These CpG dinucleotides were associated with conventional and nonconventional CpG islands. We found an overall hypermethylation of the neocentric DNA at nonconventional CpG islands that we designated as CpG islets and CpG orphans. The observed hypermethylation was consistent with the presence of a presumed transcriptionally silent chromatin state at the neocentromere. Within this neocentric chromatin, specific sites of active transcription and the centromeric chromatin boundary are defined by DNA hypomethylation. Our data demonstrate, for the first time to our knowledge, a correlation between DNA methylation and centromere formation in mammals, and that transcription and “chromatin-boundary activity” are permissible at the centromere through the selective hypomethylation of pockets of sequences without compromising the overall silent chromatin state and function of the centromere. The centromere is a chromosomal structure that is vital for the correct partitioning of chromosomes during cell division. Recent studies in a number of different species have shown that transcription is permissible within the centromere, but the mode of transcription regulation at the centromere remains unclear. DNA methylation is a well-characterized mechanism for the genomic regulation of transcription. Here, the authors investigate the relationship between DNA methylation and transcription activity at a functional human centromere. They demonstrate a high level of DNA methylation across the centromere but identify pockets of DNA sequences within the methylated domain that are non-methylated. These pockets correspond to sites of transcription and/or boundaries that separate major centromeric chromatin sub-domains. This study shows the complexity of the centromere as it uses DNA methylation to both maintain a tight chromatin structure and to allow transcription to occur.
登录
查看更多内容
影响因子：
10.5
作者：
Bartee, L;Malagnac, F;Bender, J
通讯作者：
Bender, J
影响因子：
1.6
作者：
Gisselsson, D;Shao, CB;Ehrlich, M
通讯作者：
Ehrlich, M
DOI：
10.1073/pnas.97.3.1148
发表时间：
2000-02-01
影响因子：
11.1
作者：
Howman, EV;Fowler, KJ;Choo, KHA
通讯作者：
Choo, KHA
影响因子：
4
作者：
CROSS, SH;BIRD, AP
通讯作者：
BIRD, AP
影响因子：
14.9
作者：
BIRD, AP
通讯作者：
BIRD, AP