The NF-κB Genomic Landscape in Lymphoblastoid B Cells
| Autor: | Sizun Jiang, Tommy T. Shi, Bradford Willox, Martha L. Bulyk, Manolis Kellis, Bo Zhao, Luis A. Barrera, Stefanie C.S. Schmidt, Sarah B. Mollo, Hannah Greenfeld, Benjamin E. Gewurz, Hufeng Zhou, Elliott Kieff, Kaoru Takasaki, Ellen Cahir-McFarland, Ina Ersing |
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| Přispěvatelé: | Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Barrera, Luis A., Kellis, Manolis |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Transcriptional Activation
Protein subunit Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Humans Gene Regulatory Networks Enhancer Promoter Regions Genetic lcsh:QH301-705.5 B cell 030304 developmental biology 0303 health sciences Gene knockdown B-Lymphocytes Genome Human RELB Forkhead Box Protein M1 NF-kappa B Promoter Forkhead Transcription Factors NFKB1 Molecular biology Gene Expression Regulation Neoplastic Protein Subunits medicine.anatomical_structure Enhancer Elements Genetic lcsh:Biology (General) 030220 oncology & carcinogenesis Chromatin immunoprecipitation Protein Binding |
| Zdroj: | Elsevier Open Access Cell Reports, Vol 8, Iss 5, Pp 1595-1606 (2014) |
| Popis: | The nuclear factor κB (NF-κΒ) subunits RelA, RelB, cRel, p50, and p52 are each critical for B cell development and function. To systematically characterize their responses to canonical and noncanonical NF-κB pathway activity, we performed chromatin immunoprecipitation followed by high-throughput DNA sequencing (ChIP-seq) analysis in lymphoblastoid B cell lines (LCLs). We found a complex NF-κB-binding landscape, which did not readily reflect the two NF-κB pathway paradigms. Instead, 10 subunit-binding patterns were observed at promoters and 11 at enhancers. Nearly one-third of NF-κB-binding sites lacked κB motifs and were instead enriched for alternative motifs. The oncogenic forkhead box protein FOXM1 co-occupied nearly half of NF-κB-binding sites and was identified in protein complexes with NF-κB on DNA. FOXM1 knockdown decreased NF-κB target gene expression and ultimately induced apoptosis, highlighting FOXM1 as a synthetic lethal target in B cell malignancy. These studies provide a resource for understanding mechanisms that underlie NF-κB nuclear activity and highlight opportunities for selective NF-κB blockade. National Science Foundation (U.S.). Graduate Research Fellowship |
| Databáze: | OpenAIRE |
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