Transcription Regulation of the Human Telomerase Reverse Transcriptase (hTERT) Gene.
Transcription Regulation of the Human Telomerase Reverse Transcriptase (hTERT) Gene.
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作者：
Ramlee MK;Wang J;Toh WX;Li S
胚胎干细胞和诱导多能干细胞具有通过表达称为端粒酶的酶复合物来维持其端粒长度的能力。类似地，超过85%-90%的癌细胞被发现上调端粒酶的表达，赋予它们无限增殖的潜力。端粒酶逆转录酶（Telomerase Reverse Transcriptase，TERT）是端粒酶全酶的催化亚单位，是体内端粒酶活性重建的限速因子。迄今为止，已知人端粒酶逆转录酶（hTERT）基因的表达和功能在各种分子水平（包括遗传、mRNA、蛋白质和亚细胞定位）上受到许多不同因素的调节。在这些调节手段中，转录调节是最重要的，如其在癌细胞存活以及多能干细胞维持和分化中的严格调节所示。在这里，我们讨论了hTERT基因的转录调控，主要集中在反式作用因子，如转录因子和表观遗传修饰，以及在hTERT近端启动子的遗传改变的贡献。
Embryonic stem cells and induced pluripotent stem cells have the ability to maintain their telomere length via expression of an enzymatic complex called telomerase. Similarly, more than 85%–90% of cancer cells are found to upregulate the expression of telomerase, conferring them with the potential to proliferate indefinitely. Telomerase Reverse Transcriptase (TERT), the catalytic subunit of telomerase holoenzyme, is the rate-limiting factor in reconstituting telomerase activity in vivo. To date, the expression and function of the human Telomerase Reverse Transcriptase (hTERT) gene are known to be regulated at various molecular levels (including genetic, mRNA, protein and subcellular localization) by a number of diverse factors. Among these means of regulation, transcription modulation is the most important, as evident in its tight regulation in cancer cell survival as well as pluripotent stem cell maintenance and differentiation. Here, we discuss how hTERT gene transcription is regulated, mainly focusing on the contribution of trans-acting factors such as transcription factors and epigenetic modifiers, as well as genetic alterations in hTERT proximal promoter.