Laboratory Investigation - Human/Animal Tissue

Journal of Neuro-Oncology

, Volume 104, Issue 2, pp 483-494

First online:

Epigenetic regulation of DNA methyltransferases: DNMT1 and DNMT3B in gliomas

  • Ganeshkumar RajendranAffiliated withNational Centre for Cell Science (NCCS)
  • , Karthik ShanmuganandamAffiliated withNational Centre for Cell Science (NCCS)
  • , Ameya BendreAffiliated withNational Centre for Cell Science (NCCS)
  • , Dattatreya MujumdarAffiliated withSeth GS Medical College and KEM Hospital
  • , Abhay GoelAffiliated withSeth GS Medical College and KEM Hospital
  • , Anjali ShirasAffiliated withNational Centre for Cell Science (NCCS) Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access


The role of epigenetics and significance of aberrant gene regulation in etiology of cancer is a well-established phenomenon. The hallmark of cancer epigenetics is aberrant DNA methylation consisting of global hypomethylation and regional hypermethylation of tumor suppressor genes (TSGs) by DNA methyltransferases (DNMTs). In mammals, DNA methylation is catalyzed by DNMTs encoded by DNMT1, DNMT3A, and DNMT3B. Interestingly, little is known about variation in the methylation status of epigenetic regulators themselves in gliomas. Here, we report significant overexpression of DNMT1 and DNMT3B. A study of the methylation status and histone modifications at the promoter region of DNA methyltransferase I (DNMT1) gene revealed an unmethylated DNA promoter, similar to that detected in normal brain tissues. However, a differential histone code with distinct euchromatin marks—AcH3, AcH4, and H3k4me2—was specifically detected in tumors, unlike in normal brain tissues, which were found predominantly enriched with heterochromatin marks such as H3K9me2 and H3K27me3. In contrast, a differential methylation pattern of DNMT3B gene promoter occurred in glioma tumors, wherein it was found hypomethylated. Transcriptional silencing by CpG island methylation is a prevalent mechanism for inactivation of TSGs. Inhibiting DNMTs by 5-azacytidine (DNMT inhibitor) treatment led to significant inhibition of expression of DNMT1 and DNMT3B and enhanced expression of TSGs such as PTEN and p21 analyzed in this study. Our studies have identified effects of increased presence of DNMTs on inhibition of tumor suppressors that are epigenetically silenced in gliomas, thereby leading to aberrant regulation of cell cycle progression and failure to maintain genomic stability.


Tumor suppressor genes Histone modifications Acetylation DNA methylation MS-PCR ChIP assay