25 November 2020
Methylation and regulation of cancer cells
Published online 20 April 2010
Human telomerase is a ribonucleoprotein enzyme that is usually absent or rare in normal somatic cells, but is highly expressed in cancer cells. This suggests that it plays an important role in carcinogenesis. The enzyme is composed of at least two units: an RNA component and the catalytic subunit telomerase reverse transcriptase (hTERT).
A team of researchers, led by A. Azouz from the University of Aleppo in Syria, conducted a study on the repression of transcription of the hTERT gene. It was found to have both a proximal and a distal functional domain. Modification of the proximal domain has a weak regulatory effect, but is not sufficient to repress the gene. The distal domain has a stronger role in suppressing the gene when an hTERT repressor is bound to it.
The paper suggests that methylation of hTERT can control the ability of repressors to bind to the gene. When hTERT is not methylated, repressors can bind to it and block transcription, even in the presence of transcription factors. Methylation prevents this binding, allowing the promoter to remain activated by the transcription factors.
This research shows that epigenetic modifications of the distal region of hTERT can help modulate its expression, especially in acute promyelocytic leukaemia (APL) cells in which the distal domain is usually fully methylated.