Determinants of G quadruplex-induced epigenetic instability in REV1-deficient cells.
Determinants of G quadruplex-induced epigenetic instability in REV1-deficient cells.
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DOI：
10.15252/embj.201488398
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发表时间：
2014-11-03
期刊：
影响因子：
--
通讯作者：
Sale JE
中科院分区：
文献类型：
--
作者：
Schiavone D;Guilbaud G;Murat P;Papadopoulou C;Sarkies P;Prioleau MN;Balasubramanian S;Sale JE
Rev1缺陷的鸡DT40细胞在复制形成G四链(G4)的DNA时受到损害。这会导致双亲染色质标记的局部随机丢失和基因表达的变化。我们以前曾提出，这种表观遗传不稳定性是由于G4诱导的复制叉停滞扰乱了染色质结构通过复制而准确传播的结果。在这里，我们通过证明单个G4基序导致Rev1缺陷细胞中BU-1基因座的表观遗传不稳定性来测试这一模型，尽管它距离转录起始点(TSS)3.5kb。G4的作用依赖于它驻留在前导链模板上，但与它的体外热稳定性无关。将基序从TSS移到4kb以上可以稳定基因的表达。然而，转录起始点周围的组蛋白修饰(H3K4me3和H3K9/14ac)的丢失与G4基序的位置有关，只有当启动子受到影响时才会丢失表达。这支持了这样的观点，即需要过程复制来维持组蛋白修饰模式和该模型基因座的完整转录。
REV1-deficient chicken DT40 cells are compromised in replicating G quadruplex (G4)-forming DNA. This results in localised, stochastic loss of parental chromatin marks and changes in gene expression. We previously proposed that this epigenetic instability arises from G4-induced replication fork stalls disrupting the accurate propagation of chromatin structure through replication. Here, we test this model by showing that a single G4 motif is responsible for the epigenetic instability of the BU-1 locus in REV1-deficient cells, despite its location 3.5 kb from the transcription start site (TSS). The effect of the G4 is dependent on it residing on the leading strand template, but is independent of its in vitro thermal stability. Moving the motif to more than 4 kb from the TSS stabilises expression of the gene. However, loss of histone modifications (H3K4me3 and H3K9/14ac) around the transcription start site correlates with the position of the G4 motif, expression being lost only when the promoter is affected. This supports the idea that processive replication is required to maintain the histone modification pattern and full transcription of this model locus.
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影响因子：
64.8
作者：
Cheng, MY;Bullock, CM;Zhou, QY
通讯作者：
Zhou, QY
DOI：
10.1038/nrg3296
发表时间：
2012-11
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.3
作者：
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通讯作者：
Hyrien O
影响因子：
16.8
作者：
Besnard, Emilie;Babied, Amelie;Lemaitre, Jean-Marc
通讯作者：
Lemaitre, Jean-Marc
影响因子：
16
作者：
Jasencakova, Zuzana;Scharf, Annette N. D.;Groth, Anja
通讯作者：
Groth, Anja