AI Article Synopsis
- - DNA methylation is crucial for controlling gene expression, and the enzyme Dnmt1 ensures that these methylation patterns are copied during DNA replication, aided by its interaction with Uhrf1, which identifies hemimethylated DNA segments.
- - Recent findings show that monoubiquitinated histone H3 enhances Dnmt1's effectiveness on DNA with multiple hemimethylated CpGs, indicating that ubiquitination affects Dnmt1's processivity, or its ability to efficiently modify DNA.
- - Additionally, the activity of Dnmt1 is further boosted by the Uhrf1 SRA domain, which also interacts with Dnmt1's replication focus targeting sequence, illustrating that Dnmt1 is
Article Abstract
DNA methylation controls gene expression, and once established, DNA methylation patterns are faithfully copied during DNA replication by the maintenance DNA methyltransferase Dnmt1. In vivo, Dnmt1 interacts with Uhrf1, which recognizes hemimethylated CpGs. Recently, we reported that Uhrf1-catalyzed K18- and K23-ubiquitinated histone H3 binds to the N-terminal region (the replication focus targeting sequence, RFTS) of Dnmt1 to stimulate its methyltransferase activity. However, it is not yet fully understood how ubiquitinated histone H3 stimulates Dnmt1 activity. Here, we show that monoubiquitinated histone H3 stimulates Dnmt1 activity toward DNA with multiple hemimethylated CpGs but not toward DNA with only a single hemimethylated CpG, suggesting an influence of ubiquitination on the processivity of Dnmt1. The Dnmt1 activity stimulated by monoubiquitinated histone H3 was additively enhanced by the Uhrf1 SRA domain, which also binds to RFTS. Thus, Dnmt1 activity is regulated by catalysis (ubiquitination)-dependent and -independent functions of Uhrf1.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/gtc.12732 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mechanisms of Inheritance of Chromatin States: From Yeast to Human.
Annu Rev Biophys
December 2024
Department of Biochemistry and Biophysics, University of California, San Francisco, California, USA; email:
In this article I review mechanisms that underpin epigenetic inheritance of CpG methylation and histone H3 lysine 9 methylation (H3K9me) in chromatin in fungi and mammals. CpG methylation can be faithfully inherited epigenetically at some sites for a lifetime in vertebrates and, remarkably, can be propagated for millions of years in some fungal lineages. Transmission of methylation patterns requires maintenance-type DNA methyltransferases (DNMTs) that recognize hemimethylated CpG DNA produced by replication.
View Article and Find Full Text PDFDNMT1 inhibition improves the activity of memory-like natural killer cells by enhancing the level of autophagy.
Mol Biol Rep
December 2024
Yunnan Key Laboratory of Laboratory Medicine, Yunnan Province Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China.
Background: Acute myeloid leukemia (AML) is a common hematological tumor, but it is difficult to treat. DNMT1 is a DNA methyltransferase whose main function is to maintain stable DNA methylation during the DNA replication process. DNMT1 also plays an important role in AML, but its function in cytokine-induced memory-like natural killer (CIML NK) cell activity remains unclear.
View Article and Find Full Text PDFDNMT1 prolonged absence is a tunable cellular stress that triggers cell proliferation arrest to protect from major DNA methylation loss.
Cell Mol Life Sci
December 2024
Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90128, Palermo, Italy.
Methylation of cytosine in CpG dinucleotides is an epigenetic modification carried out by DNA-methyltransferases (DNMTs) that contributes to chromatin condensation and structure and, thus, to gene transcription regulation and chromosome stability. DNMT1 maintains the DNA methylation pattern of the genome at each cell cycle by copying it to the newly synthesized DNA strand during the S-phase. DNMT1 pharmacological inhibition as well as genetic knockout and knockdown, leads to passive DNA methylation loss.
View Article and Find Full Text PDFTranscriptomic analysis and epigenetic regulators in human oocytes at different stages of oocyte meiotic maturation.
Dev Biol
December 2024
Genetics Unit, Department of Pathology, Faculty of Medicine University of Porto (FMUP), 4200-319, Portugal; CINTESIS@RISE-Health, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal. Electronic address:
Human oocytes are highly specialized cells with the capacity to store and regulate mRNAs during oocyte maturation, in preparation for post-fertilization steps. Here we performed single-oocyte transcriptomic analysis of human oocytes in three meitoic maturation stages - Germinal Vesicle (GV; n = 6), Metaphase I (MI; n = 6) and Metaphase II (MII; n = 7). Single-oocyte transcriptomic analysis revealed that the total number of expressed genes progressively decreased from GV to MII stages, with 9660 genes being transcribed in GV, 8734 in MI and 5889 in MII.
View Article and Find Full Text PDFBalancing CIK Cell Cancer Immunotherapy and PPAR Ligands: One Potential Therapeutic Application for CNS Malignancies.
Cancer Med
December 2024
Department of Integrated Oncology, Center for Integrated Oncology (CIO), University Hospital of Bonn, Bonn, Germany.
Background: Cytokine-induced killer (CIK) cell therapy has proven successful in clinical trials regarding glioblastoma. Equally important are the hints suggesting peroxisome proliferator-activated receptors (PPARs) ligands being co-expressed in the central nervous system (CNS). This provides a rationale about investigating the possible synergistic effect of CIK cells and PPARs.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!