- Genomics and Chromatin Dynamics
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- Plant nutrient uptake and metabolism
- Plant Molecular Biology Research
- Monoclonal and Polyclonal Antibodies Research
- Cancer Mechanisms and Therapy
- Chromatin Remodeling and Cancer
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
EpiCypher (United States)
2020-2024
Whitehead Institute for Biomedical Research
2018
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...
The contribution of epigenetic variation to phenotypic is unclear. Imprinted genes, because their strong association with modifications, represent an opportunity for the discovery such phenomena. In mammals and flowering plants, a subset genes are expressed from only one parental allele in process called gene imprinting. Imprinting associated differential DNA methylation chromatin modifications between alleles. plants imprinting occurs seed tissue - endosperm. Proper endosperm development...
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...
Antibodies offer a powerful means to interrogate specific proteins in complex milieu. However, antibody availability and reliability can be problematic, whereas epitope tagging impractical many cases. To address these limitations, the Protein Capture Reagents Program (PCRP) generated over thousand renewable monoclonal antibodies (mAbs) against human presumptive chromatin proteins. reagents have not been widely field-tested. We therefore performed screen test their ability enrich genomic...
The precise regulation of chromatin composition is critical to gene expression and cellular identity, thus a key component in development disease. Robust assays study features, including histone post-translational modifications (PTMs) chromatin-associated proteins (e.g., transcription factors or PTM readers), are essential understand their function identify novel therapeutic strategies. To this end, Cleavage Under Targets Release Using Nuclease (CUT&RUN) has emerged as powerful tool for...
Abstract The contribution of epigenetic variation to phenotypic is unclear. Imprinted genes, because their strong association with modifications, represent an opportunity for the discovery such phenomena. In mammals and flowering plants, a subset genes are expressed from only one parental allele in process called gene imprinting. Imprinting associated differential DNA methylation chromatin modifications between alleles. plants imprinting occurs seed tissue – endosperm. Proper endosperm...
Abstract Antibodies offer a powerful means to interrogate specific proteins in complex milieu. However, antibody availability and reliability are problematic epitope tagging can be impractical many cases. In an effort improve this situation, the Protein Capture Reagents Program (PCRP) generated over thousand renewable monoclonal antibodies (mAbs) against human-presumptive chromatin proteins. these reagents have not been widely field-tested. We therefore performed screen test their ability...
Abstract Histone post-translational modifications (PTMs) play a critical role in chromatin regulation. It has long been suspected that the poorly understood capability of ‘PTM-specific’ antibodies (i.e., their specificity and efficiency) is prime driver reproducibility crisis biomedical research. Here we confirm validity this concern as it applies to epigenomic mapping studies. Extensive spike-in panels PTM-defined DNA-barcoded nucleosome standards show >70% >500 commercial...
Abstract Chromatin remodeling, driven by ATP-dependent remodeling enzymes, plays key roles in regulating gene expression, genome replication and repair. Aberrant nucleosome organization can severely disrupt these important processes, driving various cancers developmental disorders. Remarkably, nearly 20% of all human contain mutations subunits from the SWI/SNF family chromatin complexes, making them attractive therapeutic targets interests basic research. However, studies on enzymes (and...