Back to Search
Start Over
Differential regulation of CpG island methylation within divergent and unidirectional promoters in colorectal cancer
- Source :
- Cancer Science
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- The silencing of tumor suppressor genes by promoter CpG island (CGI) methylation is an important cause of oncogenesis. Silencing of MLH1 and BRCA1, two examples of oncogenic events, results from promoter CGI methylation. Interestingly, both MLH1 and BRCA1 have a divergent promoter, from which another gene on the opposite strand is also transcribed. Although studies have shown that divergent transcription is an important factor in transcriptional regulation, little is known about its implication in aberrant promoter methylation in cancer. In this study, we analyzed the methylation status of CGI in divergent promoters using a recently enriched transcriptome database. We measured the extent of CGI methylation in 119 colorectal cancer (CRC) clinical samples (65 microsatellite instability high [MSI-H] CRC with CGI methylator phenotype, 28 MSI-H CRC without CGI methylator phenotype and 26 microsatellite stable CRC) and 21 normal colorectal tissues using Infinium MethylationEPIC BeadChip. We found that CGI within divergent promoters are less frequently methylated than CGI within unidirectional promoters in normal cells. In the genome of CRC cells, CGI within unidirectional promoters are more vulnerable to aberrant methylation than CGI within divergent promoters. In addition, we identified three DNA sequence motifs that correlate with methylated CGI. We also showed that methylated CGI are associated with genes whose expression is low in normal cells. Thus, we here provide fundamental observations regarding the methylation of divergent promoters that are essential for the understanding of carcinogenesis and development of cancer prevention strategies.
- Subjects :
- 0301 basic medicine
Cancer Research
oligonucleotide array sequence analysis
Biology
medicine.disease_cause
MLH1
Transcriptome
03 medical and health sciences
0302 clinical medicine
health services administration
mental disorders
medicine
Humans
Promoter Regions, Genetic
Genetics, Genomics, and Proteomics
Gene
Genetics
DNA methylation
Promoter
Original Articles
General Medicine
Methylation
colorectal neoplasms
digestive system diseases
humanities
Gene Expression Regulation, Neoplastic
Phenotype
030104 developmental biology
Oncology
CpG site
030220 oncology & carcinogenesis
Original Article
CpG Islands
Microsatellite Instability
Carcinogenesis
Subjects
Details
- ISSN :
- 13479032
- Volume :
- 110
- Database :
- OpenAIRE
- Journal :
- Cancer Science
- Accession number :
- edsair.doi.dedup.....6756b41d37d14c18a50f09c938df4851