A5069297803- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- RNA and protein synthesis mechanisms
- Biosensors and Analytical Detection
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Click Chemistry and Applications
- Genomics and Phylogenetic Studies
- Glycosylation and Glycoproteins Research
- Tuberculosis Research and Epidemiology
- Ubiquitin and proteasome pathways
- Bacteriophages and microbial interactions
- Immune cells in cancer
- Advanced Biosensing Techniques and Applications
- RNA regulation and disease
- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Circular RNAs in diseases
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Gene expression and cancer classification
Indiana University Health
2022-2025
Indiana University – Purdue University Indianapolis
2019-2025
Indiana University School of Medicine
2019-2024
Indiana University
2023
Van Andel Institute
2016-2020
University of Central Florida
2010-2020
DNA methylation promotes transcription generally represses transcription, but in some instances, it has also been implicated activation. Harris et al. identified a protein complex Arabidopsis that is recruited to chromatin by methylation. This specifically activated the of genes are already mildly transcribed had no effect on transcriptionally silent such as transposable elements. The thereby counteracts repression caused transposon insertion neighboring while leaving transposons silent....
The epigenetic inheritance of DNA methylation requires UHRF1, a histone- and DNA-binding RING E3 ubiquitin ligase that recruits DNMT1 to sites newly replicated through ubiquitylation histone H3. UHRF1 binds with selectivity towards hemi-methylated CpGs (HeDNA); however, the contribution HeDNA sensing function remains elusive. Here, we reveal interaction is required for but dispensable chromatin interaction, which governed by reciprocal positive cooperativity between domains. recognition...
DNA methyltransferase inhibitor (DNMTi) efficacy in solid tumors is limited. Colon cancer cells exposed to DNMTi accumulate lysine-27 trimethylation on histone H3 (H3K27me3). We propose this Enhancer of Zeste Homolog 2 (EZH2)-dependent repressive modification limits efficacy. Here, we show that low-dose treatment sensitizes colon select EZH2 inhibitors (EZH2is). Integrative epigenomic analysis reveals DNMTi-induced H3K27me3 accumulates at genomic regions poised with EZH2. Notably, combined...
Abstract Histone methyltransferase MLL4 is centrally involved in transcriptional regulation and often mutated human diseases, including cancer developmental disorders. contains a catalytic SET domain that mono-methylates histone H3K4 seven PHD fingers of unclear function. Here, we identify the PHD6 finger (MLL4-PHD6) as selective reader epigenetic modification H4K16ac. The solution NMR structure MLL4-PHD6 complex with H4K16ac peptide along binding mutational analyses reveal unique...
Elementary, Dr. Watson! A combination of YES and OR logic gates was applied to differentiate between DNA sequences wild-type rifampin-resistant (Rif(r)) Mycobacterium tuberculosis (Mtb) in a multiplex real-time fluorescent assay.
Mitotic inheritance of DNA methylation patterns is facilitated by UHRF1, a DNA- and histone-binding E3 ubiquitin ligase that helps recruit the maintenance methyltransferase DNMT1 to replicating chromatin. The function UHRF1 dependent on its ability bind chromatin, where it facilitates monoubiquitination histone H3 at lysines 18 23, docking site for DNMT1. Because technical limitations, this model UHRF1-dependent has been constructed largely based genetics biochemical observations querying...
Lysine methylation modulates the function of histone and non-histone proteins, enzymes that add or remove lysine methylation-lysine methyltransferases (KMTs) demethylases (KDMs), respectively-are frequently mutated dysregulated in human diseases. Identification sites proteome-wide has been a critical barrier to identifying substrates KMTs KDMs for studying functions methylation. Detection by mass spectrometry (MS) typically relies on enrichment methylated peptides pan-methyllysine...
Abstract Along with biocompatibility, chemical stability, and simplicity of structural prediction modification, deoxyribozyme‐based molecular sensors have the potential an improved detection limit due to their ability catalytically amplify signal. This study contributes understanding factors responsible for (LOD) RNA‐cleaving deoxyribozyme sensors. A new sensor that detects specific DNA/RNA sequences was designed from OA‐II [Chiuman, W.; Li, Y. (2006) J. Mol. Biol. 357, 748–754]. The...
In the blink of eye: A cascade two deoxyribozymes was designed for rapid visual detection bacterial 16S rRNA. The limit is 12.5 ng by naked eye, with ability to differentiate between closely related pathogenic and nonpathogenic species. As a service our authors readers, this journal provides supporting information supplied authors. Such materials are peer reviewed may be re-organized online delivery, but not copy-edited or typeset. Technical support issues arising from (other than missing...
Growing evidence shows that lysine methylation is a widespread protein post-translational modification (PTM) regulates function on histone and nonhistone proteins. Numerous studies have demonstrated the dysregulation of mediators contributes to cancer growth chemotherapeutic resistance. While changes in are well-documented with extensive analytical techniques available, there lack high-throughput methods reproducibly quantify abundances (Kme) simultaneously across multiple samples. Recent by...
The robustness of ChIP-seq datasets is highly dependent upon the antibodies used. Currently, polyclonal are standard despite several limitations: They non-renewable, vary in performance between lots and need to be validated with each new lot. In contrast, monoclonal antibody renewable provide consistent performance. To increase standardization, we investigated whether could replace antibodies. We compared that target five key histone modifications (H3K4me1, H3K4me3, H3K9me3, H3K27ac...
Mapping lysine methyltransferase substrate selectivity reveals gaps in the proteome-wide curation of methylomes.
UHRF1 is a histone- and DNA-binding E3 ubiquitin ligase that functions with DNMT1 to maintain mammalian DNA methylation. facilitates recruitment replicating chromatin through coordinated mechanism involving histone recognition ubiquitination. UHRF2 shares structural homology UHRF1, but surprisingly lacks functional redundancy facilitate methylation maintenance. Molecular mechanisms uncoupling from maintenance are poorly defined. Through comprehensive comparative biochemical analysis of...
We designed and tested a system that allows DNA logic gates to respond multiple times the addition of oligonucleotide inputs. After producing an output signal, spontaneously resets background state. This does not require any operator action achieve reset gate, may become useful for construction reusable DNA-based computational devices.
Lysine methylation is a dynamic, posttranslational mark that regulates the function of histone and nonhistone proteins. Many enzymes mediate lysine methylation, known as methyltransferases (KMTs), were originally identified to modify proteins but have also been discovered methylate In this work, we investigate substrate selectivity KMT PRDM9 identify both potential substrates. Though normally expressed in germ cells, significantly upregulated across many cancer types. The methyltransferase...
Acetylation of the histone variant H2A.Z (H2A.Zac) occurs at active regulatory regions associated with gene expression. Although Tip60 complex is proposed to acetylate H2A.Z, functional studies suggest additional enzymes are involved. Here, we show that p300 acetylates multiple lysines. In contrast, found although does not efficiently in vitro, genetic inhibition reduces H2A.Zac cells. Importantly, interaction between p300-bromodomain and H4 acetylation (H4ac) enhances p300-driven H2A.Zac....
Post-translational modifications (PTMs) on histone proteins are widely studied for their roles in regulating chromatin structure and gene expression. The mass production distribution of antibodies specific to PTMs has greatly facilitated research these marks. As PTM key reagents many biochemistry applications, rigorous analysis antibody specificity is necessary accurate data interpretation continued progress the field. This protocol describes an integrated pipeline design, fabrication use...
ChIP followed by next-generation sequencing (ChIP-Seq) is a key technique for mapping the distribution of histone posttranslational modifications (PTMs) and chromatin-associated factors across genomes. There perceived challenge to define quantitative scale ChIP-Seq data, as such, several approaches making use exogenous additives, or "spike-ins," have recently been developed. Herein, we report on development quantitative, physical model defining ChIP-Seq. The which results should be compared...
Elementar, mein lieber Watson! Eine Kombination aus YES- und OR-Logikgattern wurde eingesetzt, um DNA-Sequenzen des Wildtyps von Mycobacterium tuberculosis (Mtb) einer Rifampin-resistenten (Rifr) Mutante in einem parallelen Echtzeit-Fluoreszenzassay zu unterscheiden.