Unusual distribution of DNA methylation within the hTERT CpG island in tissues and cell lines

Unusual distribution of DNA methylation within the hTERT CpG island in tissues and cell lines
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DOI:
10.1016/j.bbrc.2004.10.137
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发表时间:
2004-12-17
影响因子:
3.1
通讯作者:
Benhattar, J
Benhattar, J
中科院分区:
生物学4区
文献类型:
--
作者:
Guilleret, I;Benhattar, J

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编码人端粒酶逆转录酶(hTERT)的基因的启动子区位于CpG岛上,并且显示至少部分地受DNA甲基化调控。然而,hTERT甲基化和基因表达之间的相关性与DNA甲基化调控的一般模型相反。我们建立了组织和细胞系中hTERT启动子周围CpG岛(-1539至+1732)甲基胞嘧啶的详细图谱。在端粒酶阳性的样本中,在hTERT启动子区(-500至+1)观察到所有CpG位点的甲基化,而外显子部分(+1至+450)显示不稳定的甲基化模式。近端外显子区域的不完全甲基化可能是必需的,至少,低水平的hTERT转录。总之,CpG岛的高甲基化在端粒酶阳性细胞中hTERT的表达中起着复杂但重要的作用。(C)2004年爱思唯尔公司All rights reserved.
The promoter region of the gene encoding the human telomerase reverse transcriptase (hTERT) is located in a CpG island and was shown to be regulated, at least in part, by DNA methylation. However, the observed correlation between hTERT methylation and gene expression was opposite to the general model of regulation by DNA methylation. We established a detailed mapping of methylcytosines at the CpG island (-1539 to +1732) surrounding the hTERT promoter in tissues and cell lines. In telomerase-positive samples, a methylation of all the CpG sites was observed for the hTERT promoter region (-500 to +1), whereas the exonic part (+1 to +450) revealed an unstable methylation pattern. Incomplete methylation of the proximal exon region could be necessary for, at least, a low level of hTERT transcription. In conclusion, hypermethylation of the CpG island plays a complex but essential role in the expression of hTERT in telomerase-positive cells. (C) 2004 Elsevier Inc. All rights reserved.