- Genomics and Chromatin Dynamics
- Chromatin Remodeling and Cancer
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Protein Degradation and Inhibitors
- Cancer-related gene regulation
- Cancer Mechanisms and Therapy
- RNA modifications and cancer
- interferon and immune responses
- RNA and protein synthesis mechanisms
- Cancer Cells and Metastasis
- Mechanisms of cancer metastasis
- Neonatal Respiratory Health Research
- Cancer-related Molecular Pathways
- Herpesvirus Infections and Treatments
- DNA Repair Mechanisms
- Animal Genetics and Reproduction
- Histone Deacetylase Inhibitors Research
- Adipose Tissue and Metabolism
- Muscle Physiology and Disorders
- Signaling Pathways in Disease
- Toxin Mechanisms and Immunotoxins
- Peroxisome Proliferator-Activated Receptors
- Ubiquitin and proteasome pathways
- Nuclear Structure and Function
University of Massachusetts Chan Medical School
2015-2024
UMass Memorial Medical Center
2023-2024
University of Massachusetts Amherst
2018
Institute for Molecular Medicine
2015
John Wiley & Sons (United States)
2015
Hudson Institute
2015
University of California, Los Angeles
2015
University of Vermont
2015
Massachusetts Academy of Math and Science
2013
Laboratoire de Biophotonique et Pharmacologie
2010
Studies of mammalian genes activated in response to an acute stimulus have suggested diverse mechanisms through which chromatin structure and nucleosome remodeling events contribute inducible gene transcription. However, because this diversity, the logical organization genome with respect induction has remained obscure. Numerous proinflammatory are rapidly induced macrophages microbial infection. Here, we show that lipopolysaccharide-stimulated macrophages, catalytic BRG1/BRM subunits...
Higher-order chromatin structure is often perturbed in cancer and other pathological states. Although several genetic epigenetic differences have been charted between normal breast tissues, changes higher-order organization during tumorigenesis not fully explored. To probe the mammary epithelial cells, we performed Hi-C analysis on MCF-10A MCF-7 cell lines. Our studies reveal that small, gene-rich chromosomes chr16 through chr22 genome display decreased interaction frequency with each...
SNF5/INI1 is a component of the ATP-dependent chromatin remodeling enzyme family SWI/SNF.Germ line mutations INI1 have been identified in children with brain and renal rhabdoid tumors, indicating that tumor suppressor.Here we report disruption Ini1 expression mice results early embryonic lethality.Ini1-null embryos die between 3.5 5.5 days postcoitum, Ini1-null blastocysts fail to hatch, form trophectoderm, or expand inner cell mass when cultured vitro.Furthermore, approximately 15%...
Alteration of nucleosomes by ATP-dependent remodeling complexes represents a critical step in the regulation transcription. The human SWI/SNF (hSWI/SNF) family is composed that contain either Brg1 or hBrm as central ATPase; however, these separate have not been compared functionally. Here we describe establishment cell lines express epitope-tagged and characterization associated with two ATPases. We show fractionates into differ activity subunit composition, whereas found one complex lower...
AbstractThe activation of muscle-specific gene expression requires the coordinated action muscle regulatory proteins and chromatin-remodeling enzymes. Microarray analysis performed in presence or absence a dominant-negative BRG1 ATPase demonstrated that approximately one-third MyoD-induced genes were highly dependent on SWI/SNF To understand mechanism activation, we chromatin immunoprecipitations analyzing myogenin promoter. We found H4 hyperacetylation preceded Brg1 binding MyoD-dependent...
The antiproliferative action of the retinoblastoma tumor suppressor protein, RB, is disrupted in majority human cancers. Disruption RB activity occurs through several disparate mechanisms, including viral oncoprotein binding, deregulated phosphorylation, and mutation gene. Here we report disruption RB-signaling cells loss a critical cooperating factor. We have previously reported that C33A fail to undergo cell cycle inhibition presence constitutively active (PSM-RB). To determine how evade...
Promoter-proximal pausing during transcriptional elongation is an important way of regulating many diverse genes, including human c-myc and c-fos, some HIV the Drosophila heat shock loci. To characterize mechanisms that regulate pausing, we have established in vitro system using hsp7O gene. We demonstrate nucleosome formation increases by >100-fold duration a pause on gene at same location as observed vivo. Readthrough this increased activator contains factor 1 (HSF1) activation domains....
The peroxisome proliferator-activated receptor gamma (PPARgamma) regulates adipogenesis, lipid metabolism, and glucose homeostasis, roles have emerged for this in the pathogenesis treatment of diabetes, atherosclerosis, cancer. We report here that induction PPARgamma activator adipogenesis forced by overexpression adipogenic regulatory proteins is blocked upon expression dominant-negative BRG1 or hBRM, ATPase subunits distinct SWI/SNF chromatin-remodeling enzymes. demonstrate histone...
Skeletal muscle differentiation requires the coordinated activity of transcription factors, histone modifying enzymes, and ATP-dependent chromatin remodeling enzymes. The type II protein arginine methyltransferase Prmt5 symmetrically dimethylates histones H3 H4 numerous nonchromatin proteins, prior work has implicated in transcriptional repression. Here we demonstrate that MyoD-induced Prmt5. One first genes activated during encodes myogenic regulator myogenin. dimethylated H3R8 (histone 3...
Dicer, an enzyme involved in microRNA (miRNA) maturation, is required for proper cell differentiation and embryogenesis mammals. Recent evidence indicates that Dicer miRNA may also regulate tumorigenesis. To better characterize the role of primary growth, we generated Dicer-conditional mice. Ablation loss mature miRNAs embryonic fibroblasts up-regulated p19Arf p53 levels, inhibited proliferation, induced a premature senescence phenotype was observed vivo after ablation developing limb adult...
The packaging of DNA into chromatin plays an important role in transcriptional regulation and nuclear processes. Brahma-related gene-1 SMARCA4 (also known as BRG1), the essential ATPase subunit mammalian SWI/SNF remodeling complex, uses energy from ATP hydrolysis to disrupt nucleosomes at target regions. Although gene promoters is well-studied, less about its higher-order genome organization. knockdown human mammary epithelial MCF-10A cells resulted 176 up-regulated genes, including many...