A5086522991- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- Genetics and Neurodevelopmental Disorders
- DNA Repair Mechanisms
- Drilling and Well Engineering
- Redox biology and oxidative stress
- Genetic Syndromes and Imprinting
- Light effects on plants
- Flavonoids in Medical Research
- Biomedical and Engineering Education
- Gene expression and cancer classification
- Computational Drug Discovery Methods
- Bacterial Genetics and Biotechnology
- Quality and Safety in Healthcare
- Pancreatic and Hepatic Oncology Research
- Escherichia coli research studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Protease and Inhibitor Mechanisms
- Neurological Disease Mechanisms and Treatments
- Hydraulic Fracturing and Reservoir Analysis
EpiCypher (United States)
2019-2024
University of North Carolina at Chapel Hill
2014
Jensen Hughes (United States)
2007
Christ University
2007
Histone post-translational modifications (PTMs) play a critical role in chromatin regulation. It has been proposed that these PTMs form localized 'codes' are read by specialized regions (reader domains) chromatin-associated proteins (CAPs) to regulate downstream function. Substantial effort made define [CAP: histone PTM] specificities, and thus decipher the code guide epigenetic therapies. However, this largely done using reductive approach of isolated reader domains peptides, which cannot...
In nucleosomes, histone N-terminal tails exist in dynamic equilibrium between free/accessible and collapsed/DNA-bound states. The latter state is expected to impact N-termini availability the epigenetic machinery. Notably, H3 tail acetylation (e.g. K9ac, K14ac, K18ac) linked increased H3K4me3 engagement by BPTF PHD finger, but it unknown if this mechanism has a broader extension. Here, we show that promotes nucleosomal accessibility other H3K4 methyl readers, importantly, extends writers,...
Histone H2A lysine 119 (H2AK119Ub) is monoubiquitinated by Polycomb repressive complex 1 and deubiquitinated deubiquitinase (PR-DUB). PR-DUB cleaves H2AK119Ub to restrict focal at target sites protect active genes from aberrant silencing. The subunits (BAP1 ASXL1) are among the most frequently mutated epigenetic factors in human cancers. How establishes specificity for over other nucleosomal ubiquitination how disease-associated mutations of enzyme affect activity unclear. Here, we determine...
Mutations in the
We report a novel platform [native capillary zone electrophoresis-top-down mass spectrometry (nCZE-TDMS)] for the separation and characterization of whole nucleosomes, their histone subunits, post-translational modifications (PTMs). As repeating unit chromatin, mononucleosomes (Nucs) are an ∼200 kDa complex DNA proteins involved in regulation key cellular processes central to human health disease. Unraveling covalent modification landscape histones defined stoichiometries within Nucs helps...
ABSTRACT Histone post-translational modifications (PTMs) play a critical role in chromatin regulation. It has been proposed that these PTMs form localized ‘codes’ are read by specialized regions (reader domains) associated proteins (CAPs) to regulate downstream function. Substantial effort made define [CAP-histone PTM] specificity, and thus decipher the histone code / guide epigenetic therapies. However, this largely done using reductive approach of isolated reader domains peptides, with...
Chromatin is more than a simple genome packaging system, and instead locally distinguished by histone post-translational modifications (PTMs) that can directly change nucleosome structure / or be ″read″ chromatin-associated proteins to mediate downstream events. An accurate understanding of PTM binding preference vital explain normal function pathogenesis, has revealed multiple therapeutic opportunities. Such studies most often use peptides, even though these cannot represent the full...
ABSTRACT In nucleosomes, histone N-terminal tails exist in dynamic equilibrium between free/accessible and collapsed/DNA-bound states. The latter state is expected to impact N-termini availability the epigenetic machinery. Notably, H3 tail acetylation ( e.g. , K9ac, K14ac, K18ac) linked increased H3K4me3 engagement by BPTF PHD finger, but it unknown if this mechanism has broader extension. Here we show that promotes nucleosomal accessibility other H3K4 methyl readers, importantly, extends...
Abstract The maintenance of gene expression patterns during metazoan development is achieved by the actions Polycomb group (PcG) complexes. An essential modification marking silenced genes monoubiquitination histone H2A lysine 119 (H2AK119Ub) deposited E3 ubiquitin ligase activity non-canonical Repressive Complex 1. Deubiquitinase (PR-DUB) complex cleaves monoubiquitin from to restrict focal H2AK119Ub at target sites and protect active aberrant silencing. BAP1 ASXL1, subunits that form...
A critical cost in future deep oil and gas recovery is the to drill a well. This dominated by rate of penetration (ROP) that becomes increasingly important with increasing depth. Improving technology drilling ROP will lower improves economics exploration development, potentially activity, production supply, lowering consumer improving economy.Industry partners U.S. Department Energy (DOE) successfully completed benchmark testing advanced diamond bits high pressure/high temperature (HP/HT)...
This study investigates the use of a canopy-connected recirculating class II type A2 biological safety cabinet (BSC) as an alternative to B2 when preparing volatile, sterile compounded preparations. Selection appropriate BSC for processes that subgram levels volatile chemicals is difficult due lack quantitative containment evidence by type. There perception hazardous compounding must be done in potential vapors, and this seeks challenge perception.In total, 5 tests, 3 prequalification tests...
Abstract NSD2 is the primary enzyme responsible for dimethylation of lysine 36 histone 3 (H3K36me2), a mark associated with active gene transcription and intergenic DNA methylation. In addition to methyltransferase domain, harbors two PWWP five PHD domains believed serve as chromatin reading modules, but their exact function in regulation activity remains underexplored. Here we report first-in-class chemical probe targeting N-terminal (PWWP1) domain NSD2. UNC6934 binds potently (K d 91 ± 8...
Abstract Nuc-MS characterizes histone modifications and variants directly from intact endogenous nucleosomes. Preserving whole nucleosome particles enables precise interrogation of their protein content, as for H3.3-containing nucleosomes which had 6-fold co-enrichment variant H2A.Z over bulk chromatin. Nuc-MS, validated by ChIP-seq, showed co-occurrence oncogenic H3.3K27M with euchromatic marks (e.g., H4K16ac >15-fold enrichment H3K79me2). By capturing the entire epigenetic landscape,...
Abstract Chromatin remodeling is mediated by ATP-dependent enzymes that play key roles regulating gene expression and genome replication/repair. Aberrant nucleosome organization from dysregulated chromatin can severely alter accessibility disrupt these important processes, thereby driving various cancers. Remarkably, nearly 20% of all human cancers contain mutations in subunits the SWI/SNF family complexes, making them great interest to basic research therapeutic intervention. In vitro...