DNA methyltransferase 1 (DNMT1) is the enzyme most responsible for epigenetic modification of human DNA and the intended target of approved cancer drugs such as 5-aza-cytidine and 5-aza-2'-deoxycytidine. 5-aza nucleosides have complex mechanisms of action that require incorporation into DNA, and covalent trapping and proteolysis of DNMT isozymes. Direct DNMT inhibitors are needed to refine unde...

Epigenetic modifications are important in tumorigenesis. The most frequent epigenetic phenomena in cancer are histone deacetylation and DNA hypermethylation, which lead to gene silencing, particularly of tumor suppressor genes. However, monotherapies with histone deacetylase (HDAC) or DNA methyltransferase (DNMT) inhibitors lack efficacy, hence there is a need to enhance their anticancer action...

Previously, we reported that long-term memory (LTM) in Aplysia can be reinstated by truncated (partial) training following its disruption by reconsolidation blockade and inhibition of PKM (Chen et al., 2014). Here, we report that LTM can be induced by partial training after disruption of original consolidation by protein synthesis inhibition (PSI) begun shortly after training. But when PSI occu...

Enzymes involved in the epigenetic regulation of the genome represent promising starting points for therapeutic intervention by small molecules, and DNA methyltransferases (DNMT) are emerging targets for the development of a new class of cancer therapeutics. In this work, we present nanaomycin A, initially identified by a virtual screening for inhibitors against DNMT1, as a compound inducing an...

We describe a large-scale random approach termed reduced representation bisulfite sequencing (RRBS) for analyzing and comparing genomic methylation patterns. BglII restriction fragments were size-selected to 500-600 bp, equipped with adapters, treated with bisulfite, PCR amplified, cloned and sequenced. We constructed RRBS libraries from murine ES cells and from ES cells lacking DNA methyltrans...

In atherosclerosis, plaques preferentially develop in arterial regions of disturbed blood flow (d-flow), which alters endothelial gene expression and function. Here, we determined that d-flow regulates genome-wide DNA methylation patterns in a DNA methyltransferase-dependent (DNMT-dependent) manner. Induction of d-flow by partial carotid ligation surgery in a murine model induced DNMT1 in arter...

Recently studies have shown that ectopic expression of activation-induced cytidine deaminase (AID) plays an important role in carcinognesis and cancer progression of inflammatory-associated cancers. Here, we examined the molecular mechanism of ectopic expression of AID in cancer cells, and whether or not nitric oxide (NO) modulates this expression, as NO is known to cause chemical deamination o...

Inhibitors of human DNA methyltransferases (DNMT) are of increasing interest to develop novel epi-drugs for the treatment of cancer and other diseases. As the number of compounds with reported DNMT inhibition is increasing, molecular docking is shedding light to elucidate their mechanism of action and further interpret structure-activity relationships. Herein, we present a structure-based ratio...

Cancer is caused by genetic as well as epigenetic changes. Chemotherapy is considered the mainstay of cancer therapy. But multiple side effects of chemotherapy has created a demand for developing other novel and specific targets for cancer therapy. The potential reversibility of epigenetic changes have resulted in the reactivation of epigenetically silenced tumor suppressor genes being an emerg...