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Series GSE96775 Query DataSets for GSE96775
Status Public on Aug 22, 2017
Title Chromatin-associated protein interactions drive megadomain formation in NUT midline carcinoma
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary To investigate the mechanism that drives dramatic mistargeting of active chromatin in NUT-midline carcinoma, we have identified protein interactions unique to the BRD4-NUT fusion oncoprotein compared to wild type BRD4. Using crosslinking, affinity purification, and mass spectrometry, we identify the p300 acetyltransferase as ectopically associated with BRD4 through the NUT fusion in both NMC and non-NMC cell types. We also identify ZNF532 among a number of candidates uniquely associated with BRD4-NUT in NMC patient cells but not present in 293T cells. p300 and ZNF532 are both implicated in feed-forward regulatory loops leading to propagation of the oncogenic regulatory complex in BRD4-NUT patient cells. Extending our biochemical findings, we independently identified a novel ZNF532-NUT translocation fusion in a newly diagnosed NMC patient. ChIP-seq of key players: NUT, ZNF532, BRD4, p300, and anti-H3K27ac, reveals the formation of ZNF532-NUT-associated hyperacetylated megadomains, distinctly localized, but otherwise analogous to those found in BRD4-NUT patient cells. Our results support a model in which NMC is caused by a cascade of misregulation that is initiated by ectopic protein-protein interactions on chromatin between NUT and several distinct, but interacting, components of BRD4 regulatory complexes.
Overall design ChIP-seq and nascent RNA sequencing of patient-derived cancer cell lines.
Contributor(s) Kharchenko P, Pakozdi T
Citation(s) 28484033
Submission date Mar 17, 2017
Last update date May 15, 2019
Contact name Peter Kharchenko
Organization name Harvard Medical School
Department DBMI
Lab Kharchenko
Street address 10 Shattuck St.
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (20)
GSM2543126 Input_24335_1
GSM2543127 Input_24335_2
GSM2543128 IP_BRD4_24335_1
BioProject PRJNA379616
SRA SRP102091

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Supplementary file Size Download File type/resource
GSE96775_RAW.tar 4.5 Gb (http)(custom) TAR (of TDF)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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