A5034494481- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- Protein Degradation and Inhibitors
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Lymphoma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- Chromosomal and Genetic Variations
- 14-3-3 protein interactions
- RNA Interference and Gene Delivery
- Glycosylation and Glycoproteins Research
- DNA Repair Mechanisms
- Gene expression and cancer classification
- Cancer-related gene regulation
- RNA modifications and cancer
- Genetic Associations and Epidemiology
- Genomic variations and chromosomal abnormalities
- Molecular Biology Techniques and Applications
- Single-cell and spatial transcriptomics
- RNA regulation and disease
- Cancer-related molecular mechanisms research
- Adipose Tissue and Metabolism
- Genetics, Bioinformatics, and Biomedical Research
Broad Institute
2011-2025
Massachusetts Institute of Technology
1994-2020
Harvard University
2015-2017
Ariadne Diagnostics (United States)
2000
Center for Cancer Research
1994-2000
University of Massachusetts Chan Medical School
1998
Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on single haploid reference genome. Here, we present the EN-TEx resource 1,635 open-access datasets from four donors (∼30 tissues × ∼15 assays). The are mapped to matched, diploid genomes with long-read phasing and structural variants, instantiating catalog >1 million allele-specific loci. These loci exhibit coordinated activity along haplotypes less conserved...
mAbs raised against the human nuclear matrix (anti-NM)1 have been used to investigate role of antigens in pre-mRNA processing. The three anti-NM this study recognize that are highly localized speckles. Surprisingly, all these preferentially immunoprecipitate splicing complexes containing exon sequences. efficiently product complex but not lariat after second step splicing. Two completely inhibit vitro. However, none appear factors stably associated with snRNPs. predominantly react distinct...
Benjamin J. Blencowe, Robbyn Issner, Jeffrey A. Nickerson, and Phillip Sharp Center for Cancer Research Department of Biology, Massachusetts Institute Technology, Cambridge, 02139 USA; Cell University Medical School, Worcester, 01655 USA
Abstract B-cell lymphomas frequently contain genomic rearrangements that lead to oncogene activation by heterologous distal regulatory elements. We used a novel approach called “pinpointing enhancer-associated chromatin immunoprecipitation,” or PEAR-ChIP, simultaneously map enhancer activity and proximal in lymphoma cell lines patient biopsies. This method detects involving known cancer genes, including CCND1, BCL2, MYC, PDCD1LG2, NOTCH1, CIITA, SGK1, as well duplication events of likely...
In a chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) experiment, an important consideration in experimental design is the minimum number of sequenced reads required to obtain statistically significant results. We present extensive evaluation impact depth on identification enriched regions for key histone modifications (H3K4me3, H3K36me3, H3K27me3 and H3K9me2/me3) using deep-sequenced datasets human fly. propose define sufficient as at which detected enrichment...
For safe clinical application of engineered cartilage made from mesenchymal stem cells (MSCs), molecular mechanisms for chondrogenic differentiation must be known in detail. Changes gene expression and extracellular matrix synthesis have been extensively studied, but the epigenomic modifications underlying these changes not described. To this end we performed whole-genome chromatin immunoprecipitation deep sequencing to quantify six histone modifications, reduced representation bisulphite...
Abstract Genome-wide association studies have associated thousands of genetic variants with complex traits and diseases, but pinpointing the causal variant(s) among those in tight linkage disequilibrium each variant remains a major challenge. Here, we use seven experimental assays to characterize all common at multiple disease-associated TNFAIP3 locus five disease-relevant immune cell lines, based on set features related regulatory potential. Trait/disease-associated are enriched SNPs...
The SRm160/300 splicing coactivator, which consists of the serine/arginine (SR)-related nuclear matrix protein 160 kDa and a 300-kDa antigen, functions in by promoting critical interactions between factors bound to pre-mRNA, including snRNPs SR family proteins. In this article we report isolation cDNA encoding antigen investigate activity it SRm160 splicing. Like SRm160, contains domains rich alternating S R residues but lacks an RNA recognition motif; is accordingly named “SRm300.” SRm300...
Small molecule-regulated transcription has broad utility and would benefit from an easily delivered self-contained regulatory cassette capable of robust, tightly controlled target gene expression. We describe the delivery a modified dimerizer-regulated expression system to cells on single retrovirus. A factor responsive natural product dimerizer rapamycin was optimized for retroviral by fusing highly potent chimeric activation domain rapamycin-binding FKBP-rapamycin-associated protein...
ABSTRACT Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on single haploid reference genome. Here, we present the EN-TEx resource personal epigenomes, for ∼25 tissues and >10 assays in four donors (>1500 open-access genomic proteomic datasets, total). Each dataset mapped to matched, diploid genome, which has long-read phasing structural variants. The mappings enable us identify >1 million loci with...
<p>Supplementary Methods, Figure Legends, Table Legends</p>