Adiponectin plays a key role in the regulation of the whole-body energy homeostasis by modulating glucose and lipid metabolism. Although obesity-induced reduction of adiponectin expression is primarily ascribed to a transcriptional regulation failure, the underlying mechanisms are largely undefined. Here we show that DNA hypermethylation of a particular region of the adiponectin promoter suppre...

Background: DNA molecule of the eukaryotic cells is found in the form of a nucleoprotein complex named chromatin. Two epigenetic modifications are critical for transcriptional control of genes, including acetylation and DNA methylation. Hypermethylation of tumor suppressor genes is catalyzed by various DNA methyltransferase enzymes (DNMTs), including DNMT1, DNMT2, and DNMT3. The most well chara...

Nasopharyngeal carcinoma (NPC) has the highest metastasis potential among head and neck cancers. Distant metastasis is the major cause of treatment failure. Recent studies from our laboratory have revealed that IL-8 promotes NPC metastasis via activation of AKT signaling and induction of epithelial-mesenchymal transition (EMT) in the cells. In the present study, we found that IL-8 treatment for...

Many CpG islands have tissue-dependent and differentially methylated regions (T-DMRs) in normal cells and tissues. To elucidate how DNA methyltransferases (Dnmts) participate in methylation of the genomic components, we investigated the genome-wide DNA methylation pattern of the T-DMRs with Dnmt1-, Dnmt3a-, and/or Dnmt3b-deficient ES cells by restriction landmark genomic scanning (RLGS). Approx...

Aberrant DNA methylation is a hallmark of acute myeloid leukemia (AML); however, the regulation of DNA methyltransferase 1 (DNMT1), which is responsible for maintenance of DNA methylation patterns, has largely remained elusive. MUC1-C is a transmembrane oncoprotein that is aberrantly expressed in AML stem-like cells. The present studies demonstrate that targeting MUC1-C with silencing or a phar...

In the developing pancreas, self-renewal of progenitors and patterning of cell fates are coordinated to ensure the correct size and cellular makeup of the organ. How this coordination is achieved, however, is not clear. We report that deletion of DNA methyltransferase 1 (Dnmt1) in pancreatic progenitors results in agenesis of the pancreas due to apoptosis of progenitor cells. We show that DNMT1...

DNA methylation is important for controlling gene expression and is catalyzed by DNA methyltransferase (Dnmt1) an enzyme abundant in brain. We recently demonstrated that mice expressing reduced levels of Dnmt1 are protected from cerebral ischemia. Here, we used the cre/loxP system to produce conditional mutants that lack Dnmt 1 in postmitotic neurons of the postnatal brain. We demonstrate that ...

Mammalian DNA methyltransferase 1 (DNMT1) is essential during early embryo development. Consistent with its key role in embryogenesis, depletion of this protein in adult somatic cells promotes severe cellular dysfunctions and cell death. DNMT1 contains a highly evolutionary conserved C-terminal catalytic DNA methyltransferase domain that is thought to be the responsible for the maintenance of C...

In mammalian cells, the replication of genetic and epigenetic information is directly coupled; however, little is known about the maintenance of epigenetic information in DNA repair. Using a laser microirradiation system to introduce DNA lesions at defined subnuclear sites, we tested whether the major DNA methyltransferase (Dnmt1) or one of the two de novo methyltransferases (Dnmt3a, Dnmt3b) ar...

BACKGROUND We use our earlier experimental studies of the catalytic mechanism of DNA methyltransferases to prepare in silico a family of novel mechanism-based inhibitors of human Dnmt1. Highly specific inhibitors of DNA methylation can be used for analysis of human epigenome and for the creation of iPS cells. RESULTS We describe a set of adenosyl-1-methyl-pyrimidin-2-one derivatives as novel ...