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| Status |
Public on Oct 01, 2015 |
| Title |
Genome-wide nucleosome dynamics in glucocorticoid-treated acute lymphoblastic leukemia cell line, RS4;11 |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Precise nucleosome positioning is an increasingly recognized feature of promoters and enhancers, reflecting complex contributions of DNA sequence, nucleosome positioning, histone modification and transcription factor binding to enhancer activity and regulation of gene expression. Changes in nucleosome position and occupancy, histone variants and modifications, and chromatin remodeling are also critical elements of dynamic transcriptional regulation, but poorly understood at enhancers. We investigated glucocorticoid receptor-associated (GR) nucleosome dynamics at enhancers in acute lymphoblastic leukemia. For the first time, we demonstrate functionally distinct modes of nucleosome remodeling upon chromatin binding by GR, which we term central, non-central, phased, and minimal. Central and non-central remodeling reflect nucleosome eviction by GR and cofactors, respectively. Phased remodeling involves nucleosome repositioning and is associated with rapidly activated enhancers and induction of gene expression. Minimal remodeling sites initially have low levels of enhancerassociated histone modification, but the majority of these regions gain H3K4me2 or H3K27Ac to become de novo enhancers. Minimal remodeling regions are associated with gene ontologies specific to decreased B cell number and mTOR inhibition and may make unique contributions to glucocorticoid-induced leukemia cell death. Our findings form a novel framework for understanding the dynamic interplay between transcription factor binding, nucleosome remodeling, enhancer function, and gene expression in the leukemia response to glucocorticoids.
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| Overall design |
We performed ChIP-Seq for histone modifications (H3K4me1, H3K4me2, H3K4me3, H3K27Ac), ChIP-Seq for transcription factors (GR and PU.1), and DNase-Seq from RS4;11 cells for two conditions: 1) no stimulation (steroid starved for 2 days), and 2) 10 nM dexamethasone for 1 hour.
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| Contributor(s) |
Wu JN, Pinello L, Yissachar E, Wischhusen JW, Yuan G, Roberts CW |
| Citation(s) |
26633995 |
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| Submission date |
Jul 31, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Jennifer Nan-Wah Wu |
| E-mail(s) |
JenniferN_Wu@dfci.harvard.edu
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| Organization name |
Dana-Farber Cancer Institute
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| Department |
Pediatric Oncology
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| Lab |
Charles W.M. Roberts
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| Street address |
450 Brookline Ave.
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (21)
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| This SubSeries is part of SuperSeries: |
| GSE71617 |
Nucleosome dynamics and gene expression in glucocorticoid-treated acute lymphoblastic leukemia, RS4;11 |
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| Relations |
| BioProject |
PRJNA291622 |
| SRA |
SRP061889 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE71616_RAW.tar |
3.9 Gb |
(http)(custom) |
TAR (of WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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