DNA Methylation Readers and Cancer: Mechanistic and Therapeutic Applications

Abstract

DNA methylation is a major epigenetic process that regulates chromatin structure which causes transcriptional activation or repression of genes in a context-dependent manner. In general, DNA methylation takes place when methyl groups are added to the appropriate bases on the genome by the action of “writer” molecules known as DNA methyltransferases. How these methylation marks are read and interpreted into different functionalities represents one of the main mechanisms through which the genes are switched “ON” or “OFF” and typically involves different types of “reader” proteins that can recognize and bind to the methylated regions. A tightly balanced regulation exists between the “writers” and “readers” in order to mediate normal cellular functions. However, alterations in normal methylation pattern is a typical hallmark of cancer which alters the way methylation marks are written, read and interpreted in different disease states. This unique characteristic of DNA methylation “readers” has identified them as attractive therapeutic targets. In this review, we describe the current state of knowledge on the different classes of DNA methylation “readers” identified thus far along with their normal biological functions, describe how they are dysregulated in cancer, and discuss the various anti-cancer therapies that are currently being developed and evaluated for targeting these proteins.

Methyl donor S-adenosylmethionine (SAM) supplementation attenuates breast cancer growth, invasion, and metastasisin vivo; therapeutic and chemopreventive applications

“…Despite that, the focus of attention for the past two decades has been on targeting hypermethylation by the administration of inhibitors of DNA methyltransferase enzyme (DNMTi). Two inhibitors, 5-Azacytidine (Vidaza®) and 5-aza-2'-deoxycytidine (Dacogen®), have already received FDA-approval for the treatment of several specific forms of myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML) and additional clinical trials are ongoing for several other cancers [ 20 , 35 ]. However, the activity of DNMTi has been limited in the case of the solid tumors largely due to toxicity and lower stability of these drugs [ 36 , 37 ].…”

“…Currently, it is used as a preventive agent for mood disorders, fibromyalgia, and joint pain. Even though the chemical structure of SAM was first described in the 1950s by Cantoni [ 19 ], its potential use as an anti-cancer therapeutic agent has only emerged over the last two decades [ 20 ]. SAM-treatment has been found to be effective in repressing the invasiveness as well as proliferative capabilities of different types of cancer cell lines [ 21 , 22 ].…”

DNA looping by two 5-methylcytosine-binding proteins quantified using nanofluidic devices

“…Our focus is probing how members of the methyl-CpG-binding domain (MBD) protein family, which share a common methyl-binding domain [7], alter the conformation of DNA molecules. Our interest arises from two lines of thought.…”

Assessment of Immuno-Histochemical Expression of MBD1 in Colorectal Adenocarcinoma and Its Correlations with Prognostic Factors

“…In human pancreatic carcinomas with lymph node metastasis, for instance, elevated expression of MBD1 has been reported. 12,13 Furthermore, knockdown of MBD1 prevented the invasion and cell proliferation of pancreatic cancer cells. 14 Whereas, in acute promyelocytic leukemia, 15 prostate cell line, and colon cancer cell lines, depressed expression of MBD1 has been reported.…”