As we know that there are few demethylating agents which you can use for hypomethylating DNA both in vitro and in vivo (for example. Azacitidine).
I wanted to do a reverse experiment to hypermethylate DNA and cant find a good reference.
Thanks
Bish
Dear Bishwanath,
The following paper covers the answer to your question:
Original Paper
Cell Death and Differentiation (2014) 21, 761–773; doi:10.1038/cdd.2013.202; published online 24 January 2014
DNA hypermethylation in prostate cancer is a consequence of aberrant epithelial differentiation and hyperproliferation
D Pellacani1, D Kestoras1, A P Droop1, F M Frame1, P A Berry1, M G Lawrence2, M J Stower3, M S Simms4,5, V M Mann4,5, A T Collins1, G P Risbridger2 and N J Maitland1
Abstract
Prostate cancer (CaP) is mostly composed of luminal-like differentiated cells, but contains a small subpopulation of basal cells (including stem-like cells), which can proliferate and differentiate into luminal-like cells. In cancers, CpG island hypermethylation has been associated with gene downregulation, but the causal relationship between the two phenomena is still debated. Here we clarify the origin and function of CpG island hypermethylation in CaP, in the context of a cancer cell hierarchy and epithelial differentiation, by analysis of separated basal and luminal cells from cancers. For a set of genes (including GSTP1) that are hypermethylated in CaP, gene downregulation is the result of cell differentiation and is not cancer specific. Hypermethylation is however seen in more differentiated cancer cells and is promoted by hyperproliferation. These genes are maintained as actively expressed and methylation-free in undifferentiated CaP cells, and their hypermethylation is not essential for either tumour development or expansion. We present evidence for the causes and the dynamics of CpG island hypermethylation in CaP, showing that, for a specific set of genes, promoter methylation is downstream of gene downregulation and is not a driver of gene repression, while gene repression is a result of tissue-specific differentiation.
Discussion
CpG island hypermethylation has been demonstrated in all cancer types at multiple genomic loci. Because of its early appearance and frequency, it is thought to be one of the cancer’s founding alterations and thus occurs in the cancer cell of origin, potentially even before DNA mutation. In all cancers, including CaP, hypermethylation is responsible for the downregulation of tumour suppressor genes,16 promoting both cancer development and progression. However, the mechanisms by which CpG island hypermethylation originates in cancer are still poorly understood. Here we show a direct link between tissue-specific differentiation, gene downregulation and hypermethylation in CaP. In order to dissect intra-tumour cellular heterogeneity, we have analysed primary prostate basal and luminal cells derived from BPH and CaP separately. In this way, we identified a set of genes (DAH) frequently hypermethylated in CaP, which is primarily downregulated through tissue-specific differentiation, both in normal tissues and cancer. For these genes, we hypothesize that DNA methylation can arise only after gene downregulation and is aided by cell hyperproliferation. Moreover, downregulation and hypermethylation of these genes are not essential for either tumour development or expansion.
To view the full paper, please see attached file.
Hoping this will be helpful,
Rafik
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