DNA methyltransferase 1 (Dnmt1) reestablishes methylation of hemimethylated CpG sites generated during DNA replication in mammalian cells. Two subdomains, the proliferating cell nuclear antigen (PCNA)-binding domain (PBD) and the targeting sequence (TS) domain, target Dnmt1 to the replication sites in S phase. We aimed to dissect the details of the cell cycle-dependent coordinated activity of b...

Epigenetic modifications play an important role during carcinogenesis. The main goal of this study was to examine expression levels of two critical enzymes, DNA methyltransferase-1 (DNMT1) and histone deacetylase-1 (HDAC1), by immunohistochemistry (IHC) in human pancreatic cancer and precancerous lesions: 20 foci containing normal ductal epithelial cells without an inflammatory back-ground (DE)...

The cytosine analogue decitabine alters hematopoietic differentiation. For example, decitabine treatment increases self-renewal of normal hematopoietic stem cells. The mechanisms underlying decitabine-induced shifts in differentiation are poorly understood, but likely relate to the ability of decitabine to deplete the chromatin-modifying enzyme DNA methyltransferase 1 (DNMT1), which plays a cen...

Obesity is a grave disease that is increasing in global prevalence. Aberrant neuronal DNA methylation patterns have been implicated in the promotion of obesity development, but the role of neuronal DNA methyltransferases (Dnmts; enzymes that catalyze DNA methylation) in energy balance remains poorly understood. We investigated the role of neuronal Dnmt1 in normal energy regulation and obesity d...

DNA methylation serves as the principal form of post-replicative epigenetic modification. It is intricately involved in gene regulation and silencing in eukaryotic cells, making significant contributions to cell phenotype. Much of it is mitotically inherited; some is passed on from one filial generation to the next. Establishment and maintenance of DNA methylation patterns in mammals is governe...

Small interfering RNAs (siRNAs) are newly identified molecules shown to silence genes via targeted mRNA degradation. In this study, we used specific siRNAs as a tool to probe the relationship between two DNA methyltransferase genes, DNMT3b and DNMT1, in the maintenance of DNA methylation patterns in the genome. Levels of DNMT3b or DNMT1 mRNAs and proteins were markedly decreased (up to 80%) on ...

Deletion analysis of mouse DNMT1, the primary maintenance methyltransferase in mammals, showed that most of the N-terminal regulatory domain (amino acid residues 412-1112) is required for its enzymatic activity. Although analysis of deletion mutants helps to identify regions of a protein sequence required for a particular activity, amino acid deletions can have drastic effects on protein struct...

Eukaryotic genomes are methylated at cytosine bases in the context of CpG dinucleotides, a pattern which is maintained through cell division by the DNA methyltransferase Dnmt1. Dramatic methylation losses are observed in plant and mouse cells lacking Lsh (lymphoid specific helicase), predominantly at repetitive sequences and gene promoters. However, the mechanism by which Lsh contributes to the...

Berberine (BBR), one of active alkaloid found in the rhizome, exhibited anti-cancer properties. We have showed that BBR inhibited growth of non-small cell lung cancer (NSCLC) cells through mitogen-activated protein kinase (MAPK)-mediated increase in forkhead box O3a (FOXO3a). However, the in-depth mechanism underlying the anti-tumor effects still remained to be elucidated. Herein, we further co...

Alteration of aberrant DNA methylation is one of the most consistent epigenetic changes found in human cancers. DNA methylation is catalyzed by DNA methyltransferase (DNMT). In this study, we examined DNMT protein expression by immunohistochemistry in surgically resected hepatocellular carcinomas (HCCs). Sections of paraffin-embedded specimens were obtained from 95 patients with HCC between 198...