Site-specific methylation of CpG nucleotides in the hTERT promoter region can control the expression of hTERT during malignant progression of colorectal carcinoma.
Expression of hTERT has been recognized an important factor in cellular aging and immortalization. Therefore, to analyze regulatory mechanism of hTERT expression, we investigated the CpG methylation pattern of the hTERT promoter as an epigenetic mechanism and its implication in transcriptional regulation of hTERT using tissues of colorectal carcinoma. As a result, we were able to observe an increased pattern of hTERT expression according to the malignant progression of colorectal carcinoma. Additionally, we could find that hTERT expression was induced when the P1 and P2 region of hTERT were sufficiently hypermethylated and, oppositely, the G1 region of hTERT was hypomethylated. Importantly, we could find three specific CpG sites (7th CpG of P2 and 11th and 2nd-10th CpGs of P1) closely related with the increasing of hTERT expression. These findings may provide important clues to deducing the expression mechanisms of hTERT.
Department of Laboratory Medicine, College of Medicine, Chung-Ang University, 221 Heuksuk-Dong, Dongjak-Ku, Seoul 156-756, South Korea.
Jee-Hye
JH
Choi
Soo Hyun
SH
Park
Jina
J
Park
Borae G
BG
Park
Seong-Jae
SJ
Cha
Kwang-Hoon
KH
Kong
Kwang-Ho
KH
Lee
Ae Ja
AJ
Park
D001665:Binding Sites; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics* / Q000502:physiology; D003596:Cytosine / Q000378:metabolism; D019175:DNA Methylation; D015257:DNA-Cytosine Methylases / Q000378:metabolism; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008957:Models, Genetic; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism
D012313:RNA; D003596:Cytosine; D015257:DNA-Cytosine Methylases; C509186:TERT protein, human; D019098:Telomerase