A5050437003- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- Genetic Syndromes and Imprinting
- RNA modifications and cancer
- Genetics and Neurodevelopmental Disorders
- Cancer-related gene regulation
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Acute Myeloid Leukemia Research
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Enzyme Structure and Function
- Signaling Pathways in Disease
- Synthetic Organic Chemistry Methods
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- DNA Repair Mechanisms
- Hemoglobinopathies and Related Disorders
- Microbial Community Ecology and Physiology
- DNA and Nucleic Acid Chemistry
- Microtubule and mitosis dynamics
- Renal and related cancers
- Microbial bioremediation and biosurfactants
- Biomedical Ethics and Regulation
- Insect symbiosis and bacterial influences
- Genomics and Phylogenetic Studies
New York University
2011-2025
NYU Langone Health
2020
Molecular Research Institute
2020
Boston Children's Hospital
2010-2011
Cancer Institute (WIA)
2011
Harvard University
2000-2010
Brigham and Women's Hospital
2007
Beth Israel Deaconess Medical Center
2005
Massachusetts General Hospital
2005
Methylation Mediation of cytosine bases, 5-methylcytosine (5mC), in DNA plays an important regulatory role mammalian genomes. patterns are often inherited across generations, but they can also be dynamic, suggesting that active demethylation pathways exist. One such pathway, best characterized plants, involves the removal 5mC base, and its replacement by C, via a repair mechanism. Kriaucionis Heintz (p. 929 , published online 16 April) now show that, as well genomes, there significant...
Background We recently showed that enzymes of the TET family convert 5-mC to 5-hydroxymethylcytosine (5-hmC) in DNA. 5-hmC is present at high levels embryonic stem cells and Purkinje neurons. The methylation status cytosines typically assessed by reaction with sodium bisulfite followed PCR amplification. Reaction promotes cytosine deamination, whereas 5-methylcytosine (5-mC) reacts poorly resistant deamination. Since yield 5-methylenesulfonate (CMS), we asked how DNA containing behaves...
Modified bases in nucleic acids present a layer of information that directs biological function over and beyond the coding capacity conventional bases. While large number modified have been identified, many enzymes generating them still remain to be discovered. Recently, members 2-oxoglutarate- iron(II)-dependent dioxygenase superfamily, which modify diverse substrates from small molecules biopolymers, were predicted subsequently confirmed catalyze oxidative modification acids. Of these, two...
The Tet family of methylcytosine dioxygenases (Tet1, Tet2, and Tet3) convert 5-methylcytosine to 5-hydroxymethylcytosine. To date, functional overlap among members has not been examined systematically in the context embryonic development. clarify potential for enzymes during development, we mutated zebrafish orthologs Tet1, Tet3 single-, double-, triple-mutant genotypes. Here, identify Tet2 as major embryo uncover a combined requirement hematopoietic stem cell (HSC) emergence. We demonstrate...
Significance A prominent epigenetic mechanism for gene regulation is methylation of cytosine bases in DNA. TET enzymes facilitate DNA demethylation by converting 5-methylcytosine (5mC) to oxidized methylcytosines (oxi-mCs). We show that oxi-mCs are generated conserved TET/JBP encoded the genome model organism Coprinopsis cinerea and present a method simultaneous mapping three different species at near–base-pair resolution. observe centromeres transposable elements exhibit distinctive...
Cultured pluripotent cells accumulate detrimental chromatin alterations, including DNA methylation changes at imprinted genes known as loss of imprinting (LOI). Although the occurrence LOI is considered a stochastic phenomenon, here we document genetic determinant that segregates mouse into stable and unstable cell lines. Unstable lines exhibit hypermethylation Dlk1-Dio3 other loci, in addition to impaired developmental potential. Stimulation demethylases by ascorbic acid prevents...
Tandem-repetitive DNA (where two or more bases are repeated numerous times) can adopt non-canonical secondary structures. Many of these structures implicated in important biological processes. Human Satellite III (HSat3) is enriched for tandem repeats the sequence ATGGA and located pericentromeric heterochromatin many human chromosomes. Here, we investigate structure four-repeat HSat3 5'-ATGGA ATGGA-3' using X-ray crystallography, NMR, biophysical methods. Circular dichroism spectroscopy,...
Abstract Cancer cells, aging and cells from patients with the developmental disorder Immunodeficiency, C entromeric instability, F acial anomalies (ICF) syndrome frequently display a striking loss of DNA methylation (hypomethylation) that is accompanied by increased damage chromosomal rearrangements. Despite robust link, mechanism which hypomethylation leads to genomic instability poorly understood. We report human pericentromeric repeat sequence Satellite 2 (SAT2) poses challenges...
Naïve pluripotent stem cells (nPSC) frequently undergo pathological and not readily reversible loss of DNA methylation marks at imprinted gene loci. This abnormality poses a hurdle for using cell lines in biomedical applications underscores the need to identify causes imprint instability these cells. We show that nPSCs from inbred mouse strains exhibit pronounced strain-specific susceptibility locus-specific deregulation imprinting during reprogramming pluripotency upon culture with MAP...
Summary Cultured pluripotent cells accumulate detrimental epigenetic alterations, including DNA methylation changes at imprinted genes known as loss-of-imprinting (LOI). Despite the substantial biomedical relevance of this phenomenon, molecular cause instability in remains unknown. While occurrence LOI is generally considered a stochastic here we document strong genetic determinant that segregates mouse into epigenetically stable and unstable cell lines. Unstable lines exhibit...