端粒酶表現以及端粒長度的維持對於細胞增生以及生長非常重要，並且牽涉到發育、老化以及癌症的發生。在人類細胞中影響端粒酶活性的主要機制是透過調控具有酵素活性的端粒反轉錄酶 hTERT基因轉錄表現。已有許多轉錄因子被發現能直接或間接的調控hTERT的啟動子，例如c-Myc、Sp1、ER、Ets、AP1、E2Fs 以及 p53。最近有文獻提出，在癌症細胞中MBD1的結合因子MCAF1能參與在Sp1所調控的端粒酶活性，當MCAF1與Sp1被抑制表現時，TERT的表現將會下降，並減弱端粒酶活性。首先我們先觀察到大量表現MCAF1蛋白質在細胞中，其免疫螢光染色訊號會呈現異染色質的分佈情形，有趣的是部份的MCAF1訊號會與內生性的PML-NBs重疊。我們接著證明MCAF1能夠促進hTERT的基因轉錄活性，且當MCAF1被抑制表現時能夠抑制啟動子的轉錄活性。此外，我們發現在hTERT啟動子上的Sp1結合位置突變將降低MCAF1促進hTERT的基因轉錄活性，顯示MCAF1需要透過Sp1調控hTERT的啟動子。重要的是，大量表現PML將抑制MCAF1所促進的hTERT基因轉錄活性，並且由免疫螢光染色的結果發現，大量表現的PML會將MCAF1召集至PML-NBs中。我們的實驗結果顯示PML能夠調節MCAF1/Sp1所促進的hTERT基因轉錄表現。

Telomerase expression and telomere maintenance are critical for cell proliferation and survival, which play important roles in development, aging, and cancer. The major mechanism to regulate telomerase activity in human cells is transcriptional control of the catalytic subunit, human telomerase reverse transcriptase gene hTERT. Numerous factors have been identified to directly or indirectly regulate the hTERT promoter, including cellular transcriptional factors c-Myc, Sp1, ER, Ets, AP1, E2Fs and p53. Recent studies have indicated that MCAF1 (MBD1-containing chromatin-associated factor 1) was involved in Sp1-mediated maintenance of telomerase activity in cancer cells. Depletion of MCAF1 or Sp1 down-regulated TERT gene expression resulting in decreased telomerase activity. Initially, we find that ectopic expression of MCAF1 is enriched in heterochromatin foci and interestingly, showing partially merged signals with endogenous PML nuclear bodies (PML-NBs). We first demonstrate that overexpression of MCAF1 promotes TERT-mediated promoter activity whereas knockdown of endogenous MCAF1 expression by RNA interference decreases promoter activity. Furthermore, we show that Sp1 binding site deletion mutants in hTERT promoter reduces the transcriptional activation by MCAF1, indicating that MCAF1 activates expression of hTERT through Sp1. Importantly, overexpression of PML can suppress MCAF1-mediated transactivation of the TERT promoter. Moreover, immunofluorescence analysis shows that PML overexpression resulting in a translocation of MCAF1 to the PML-NBs. Our findings therefore reveal a novel regulatory role for the PML in modulating MCAF1/Sp1 stimulated TERT transcription activation.

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