Histone deacetylation is involved in the transcriptional repression of hTERT in normal human cells
Histone deacetylation is involved in the transcriptional repression of hTERT in normal human cells
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DOI：
10.1074/jbc.c000637200
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发表时间：
2000-11-17
影响因子：
4.8
通讯作者：
Bacchetti, S
中科院分区：
文献类型：
--
作者：
Cong, YS;Bacchetti, S
人类端粒酶逆转录酶（hTERT）基因的转录调控，编码人类端粒酶的催化蛋白，在细胞永生化和肿瘤发生过程中对酶的激活起着至关重要的作用。然而，参与调控hTERT表达的分子机制尚不完全清楚。我们之前已经克隆并鉴定了hTERT基因的基因组序列和启动子。在这里，我们提供的证据表明，组蛋白去乙酰化参与了人类细胞中hTERT的抑制。曲古抑素A抑制端粒酶阴性细胞的组蛋白去乙酰化酶，导致端粒酶活性激活和hTERT mRNA表达上调。在hTERT启动子控制下的瞬时转染实验表明，该启动子可以被曲古霉素a激活。最后，我们的研究结果表明，Mad蛋白抑制hTERT启动子需要组蛋白去乙酰化酶活性，而曲古霉素a的去抑制与位于其核心区域的e- box无关。
Trancriptional regulation of the human telomerase reverse transcriptase (hTERT) gene, encoding the catalytic protein of human telomerase, plays a critical role in the activation of the enzyme during cell immortalization and tumorigenesis. However, the molecular mechanisms involved in the regulation of hTERT expression are still not fully understood. We have previously cloned and characterized the genomic sequences and promoter of the hTERT gene. Here, we provide evidence that histone deacetylation is involved in the repression of hTERT in human cells. Inhibition of histone deacetylases by trichostatin A in telomerase-negative cells resulted in activation of telomerase activity and upregulation of hTERT mRNA. Transient transfection experiments with a reporter under control of the hTERT promoter indicated that this promoter can be activated by trichostatin A. Finally, our results show that repression of the hTERT promoter by the Mad protein requires histone deacetylase activity, whereas de-repression by trichostatin A is independent of the E-boxes located in its core region.