A5033843763- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Estrogen and related hormone effects
- Ubiquitin and proteasome pathways
- NF-κB Signaling Pathways
- Steroid Chemistry and Biochemistry
- Hormonal Regulation and Hypertension
- Microtubule and mitosis dynamics
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Genetic factors in colorectal cancer
- interferon and immune responses
- Immune Response and Inflammation
- Adrenal Hormones and Disorders
- RNA and protein synthesis mechanisms
- Immune cells in cancer
National Institutes of Health
2021-2024
National Cancer Institute
2021-2023
Protein Express (United States)
2022
Stowers Institute for Medical Research
2016-2019
The Open University
2016-2019
The cohesin complex is central to chromatin looping, but mechanisms by which these long-range interactions are formed and persist remain unclear. We demonstrate that between a transcription factor (TF) the loader NIPBL regulate enhancer-dependent gene activity. Using mass spectrometry, genome mapping, single-molecule tracking methods, we glucocorticoid (GC) receptor (GR) interacts with at level, promoting loop extrusion regulation. Real-time experiments show loss of markedly diminishes...
FACT (facilitates chromatin transcription) is an evolutionarily conserved histone chaperone that was initially identified as activity capable of promoting RNA polymerase II (Pol II) transcription through nucleosomes in vitro. In this report, we describe a global analysis function Pol Drosophila. We present evidence loss has dramatic impact on elongation-coupled processes including H3 lysine 4 (H3K4) and H3K36 methylation, consistent with role for coordinating modification architecture during...
Abstract The glucocorticoid receptor (GR) is a ubiquitously expressed transcription factor that controls metabolic and homeostatic processes essential for life. Although numerous crystal structures of the GR ligand-binding domain (GR-LBD) have been reported, functional oligomeric state full-length receptor, which its transcriptional activity, remains disputed. Here we present five new agonist-bound GR-LBD, along with thorough analysis previous structural work. We identify four distinct...
Cancers often display immune escape, but the mechanisms are incompletely understood. Herein, we identify SMYD3 as a mediator of escape in human papilloma virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC), an aggressive disease with poor response to immunotherapy pembrolizumab. depletion induces upregulation multiple type I interferon (IFN) antigen presentation machinery genes HNSCC cells. Mechanistically, binds regulates transcription UHRF1, encoding for reader H3K9me3,...
The tumor-suppressing function of SMAD4 is frequently subverted during mammary tumorigenesis, leading to cancer growth, invasion, and metastasis. A long-standing concept that not regulated by phosphorylation but ubiquitination. Our search for signaling pathways breast tumor kinase (BRK), a nonreceptor protein tyrosine up-regulated in ~80% invasive ductal tumors, led us find BRK competitively binds phosphorylates regulates transforming growth factor-β/SMAD4 pathway. constitutively active...
Abstract Disclosure: T. Tettey: None. S. Kim: K. Wagh: Q. Lao: L.R. Schiltz: D.A. Stavreva: D.M. Presman: D.P. Merke: G.L. Hager: The glucocorticoid receptor (GR) is a hormone regulated transcription factor which binds chromatin to regulate many genes, including stress-response and inflammatory genes. Dexamethasone, GR agonist, widely used in the treatment of severe inflammation, COVID-19. vital for life several mutations have been linked pathophysiological conditions. Here we report novel...
Abstract The glucocorticoid receptor (GR) is a ubiquitously expressed transcription factor that controls metabolic and homeostatic processes essential for life. Although numerous crystal structures of the GR ligand-binding domain (GR-LBD) have been reported, functional oligomeric state full-length receptor, which its transcriptional activity, remains disputed. Here we present five new agonist-bound GR-LBD, along with thorough analysis previous structural work. Biologically relevant...
The highly conserved histone chaperone FACT ( Fa cilitates C hromatin T ranscription) is thought to contribute the disassembly and reassembly of nucleosomes in wake RNA polymerase II passage through chromatin. In yeast, mutation subunits leads decreased nucleosome occupancy at promoters transcribed regions genes. addition, genetic experiments suggest that yeast plays a critical role restricting initiation transcription normal promoters, ensuring only appropriate mRNAs are synthesized....
SUMMARY Cancers often display immune escape, but the mechanisms and potential for reversibility are incompletely understood. Epigenetic dysregulation has been implicated in escape of various cancer types. We have identified epigenetic modifier SET MYND-domain containing protein 3 (SMYD3) as a mediator human papilloma virus (HPV)- negative head neck squamous cell carcinoma (HNSCC), an aggressive disease with poor prognosis low response to immunotherapy pembrolizumab, programmed-death-1 (PD-1)...