Senescent cells harbour features of the cancer epigenome.
Senescent cells harbour features of the cancer epigenome.
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DOI：
10.1038/ncb2879
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发表时间：
2013-12
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
--
作者：
DNA 甲基化的改变以及相关的基因组完整性和功能的不稳定是癌症的标志。复制衰老是一种肿瘤抑制过程，它限制了正常细胞的增殖潜力，所有癌细胞都必须绕过这一限制。在这里，我们通过全基因组单核苷酸亚硫酸氢盐测序表明，复制性衰老人类细胞表现出广泛的DNA低甲基化和局灶性高甲基化。低甲基化优先发生在基因贫乏、复制晚期、核纤层蛋白相关结构域，并与接近衰老的细胞中维持 DNA 甲基转移酶 (DNMT1) 的错误定位有关。低水平的甲基化在 CpG 岛中富集，包括那些甲基化和沉默被认为会促进癌症的基因。因此，复制性衰老中甲基化的获得和丧失在性质上与癌症中的甲基化相似，并且当细胞绕过衰老时，这种“重新编程”的甲基化景观在很大程度上得以保留。因此，如果衰老细胞逃脱增殖屏障，其 DNA 甲基化可能会促进恶性肿瘤。
Altered DNA methylation and associated destabilization of genome integrity and function is a hallmark of cancer. Replicative senescence is a tumour suppressor process that imposes a limit on the proliferative potential of normal cells that all cancer cells must bypass. Here we show by whole-genome single-nucleotide bisulfite sequencing that replicative senescent human cells exhibit widespread DNA hypomethylation and focal hypermethylation. Hypomethylation occurs preferentially at gene-poor, late-replicating, lamin-associated domains and is linked to mislocalization of the maintenance DNA methyltransferase (DNMT1) in cells approaching senescence. Low-level gains of methylation are enriched in CpG islands, including at genes whose methylation and silencing is thought to promote cancer. Gains and losses of methylation in replicative senescence are thus qualitatively similar to those in cancer, and this ‘reprogrammed’ methylation landscape is largely retained when cells bypass senescence. Consequently, the DNA methylome of senescent cells might promote malignancy, if these cells escape the proliferative barrier.
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影响因子：
16
作者：
Chandra, Tamir;Kirschner, Kristina;Thuret, Jean-Yves;Pope, Benjamin D.;Ryba, Tyrone;Newman, Scott;Ahmed, Kashif;Samarajiwa, Shamith A.;Salama, Rafik;Carroll, Thomas;Stark, Rory;Janky, Rekin's;Narita, Masako;Xue, Lixiang;Chicas, Agustin;Nunez, Sabrina;Janknecht, Ralf;Hayashi-Takanaka, Yoko;Wilson, Michael D.;Marshall, Aileen;Odom, Duncan T.;Babu, M. Madan;Bazett-Jones, David P.;Tavare, Simon;Edwards, Paul A. W.;Lowe, Scott W.;Kimura, Hiroshi;Gilbert, David M.;Narita, Masashi
通讯作者：
Narita, Masashi
影响因子：
50.3
作者：
De Carvalho DD;Sharma S;You JS;Su SF;Taberlay PC;Kelly TK;Yang X;Liang G;Jones PA
通讯作者：
Jones PA
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
56.9
作者：
Gaudet, F;Hodgson, JG;Jaenisch, R
通讯作者：
Jaenisch, R