DNA cytosine methylation is an epigenetic modification involved in the transcriptional repression of genes controlling a variety of physiological processes, including hematopoiesis. DNA methyltransferase 1 (Dnmt1) is a key enzyme involved in the somatic inheritance of DNA methylation and thus plays a critical role in epigenomic stability. Aberrant methylation contributes to the pathogenesis of ...

tt D ow nladed fom DNA methyltransferase 1 (DNMT1) is the primary enzyme that maintains DNA methylation. We describe a previously unknown mode of regulation of DNMT1 protein stability through the coordinated action of an array of DNMT1-associated proteins. DNMT1 was destabilized by acetylation by the acetyltransferase Tip60, which triggered ubiquitination by the E3 ligase UHRF1, thereby targeti...

Mammalian DNA methyltransferase 1 (DNMT1) is essential for maintaining DNA methylation patterns after cell division. Disruption of DNMT1 catalytic activity results in whole genome cytosine demethylation of CpG dinucleotides, promoting severe dysfunctions in somatic cells and during embryonic development. While these observations indicate that DNMT1-dependent DNA methylation is required for prop...

DNA methylation is an important epigenetic mark that regulates gene expression. Dnmt1 plays an important role in maintaining DNA methylation patterns on daughter DNA strands. Studies have shed light into the functional role of Dnmt1 regulation in the hematopoietic and epidermal systems. Here we show that Dnmt1 is required for myogenesis. Loss of Dnmt1 results in reduced expression of myogenic g...

Somatic changes in CpG dinucleotide methylation occur quite commonly in human cancer cell DNA. Relative to DNA from normal human colonic cells, DNA from human colorectal cancer cells typically displays regional CpG dinucleotide hypermethylation amid global CpG dinucleotide hypomethylation. The role of the maintenance DNA methyltransferase (DNMT1) in the acquisition of such abnormal CpG dinucleo...

Several mammalian proteins involved in chromatin and DNA modification contain CXXC zinc finger domains. We compared the structure and function of the CXXC domains in the DNA methyltransferase Dnmt1 and the methylcytosine dioxygenase Tet1. Sequence alignment showed that both CXXC domains have a very similar framework but differ in the central tip region. Based on the known structure of a similar...

8 Aberrant activation of the Wnt signaling pathway is an 9 important step in the initiation and progression of tumor 10 development in diverse cancers. The central effector of canon11 ical Wnt signaling, b-catenin (CTNNB1), is a multifunctional 12 protein, and has been extensively studied with respect to its 13 roles in cell–cell adhesion and in regulation of Wnt-driven 14 transcription. Here, ...

Dnmt1 is critical for immediate postnatal intestinal development, but is not required for the survival of the adult intestinal epithelium, the only rapidly dividing somatic tissue for which this has been shown. Acute Dnmt1 deletion elicits dramatic hypomethylation and genomic instability. Recovery of DNA methylation state and intestinal health is dependent on the de novo methyltransferase Dnmt3...

Nicotinamide adenine dinucleotide (NAD) is a crucial molecule of energy production and signal transduction processes that have been linked to ovarian cancer development. Notably, emerging evidence has led to considerable interest in the role of DNA methyltransferase 1 (DNMT1) in the initiation and progression of ovarian cancer. However, dynamic crosstalk between NAD and DNMT1 is poorly understo...

DNA methylation is an epigenetic mark critical for regulating transcription, chromatin structure and genome stability. Although many studies have shed light on how methylation impacts transcription and interfaces with the histone code, far less is known about how it regulates genome stability. We and others have shown that DNA methyltransferase 1 (DNMT1), the maintenance methyltransferase, cont...