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Series GSE233301 Query DataSets for GSE233301
Status Public on May 24, 2023
Title Molecular features driving condensate formation and gene expression by the BRD4-NUT fusion oncoprotein are overlapping but distinct [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Aberrant formation of biomolecular condensates has been proposed to play a role in several cancers. The oncogenic fusion protein BRD4-NUT forms condensates and drives changes in gene expression in Nut Carcinoma (NC). Here we sought to understand the molecular elements of BRD4-NUT and its associated histone acetyltransferase (HAT), p300, that promote these activities. We determined that a minimal fragment of NUT (MIN) in fusion with BRD4 is necessary and sufficient to bind p300 and form condensates. Furthermore, a BRD4-p300 fusion protein also forms condensates and drives gene expression similarly to BRD4-NUT(MIN), suggesting the p300 fusion may mimic certain features of BRD4-NUT. The intrinsically disordered regions, transcription factor-binding domains, and HAT activity of p300 all collectively contribute to condensate formation by BRD4-p300, suggesting that these elements might contribute to condensate formation by BRD4-NUT. Conversely, only the HAT activity of BRD4-p300 appears necessary to mimic the transcriptional profile of cells expressing BRD4-NUT. Our results suggest a model for condensate formation by the BRD4-NUT:p300 complex involving a combination of positive feedback and phase separation, and show that multiple overlapping, yet distinct, regions of p300 contribute to condensate formation and transcriptional regulation.
 
Overall design Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for HEK293 T-Rex Flp-In - based stable cell lines, expressing BRD4-NUT, BRD4-NUT(MIN) or BRD4-p300, in a doxycycline-inducible manner. ChIP-seq performed using anti-NUT antibody for BRD4-NUT and BRD4-NUT(MIN) - expressing cell lines. ChIP-seq performed using anti-histone H3K27 acetyl antibody for BRD4-NUT(MIN) and BRD4-p300 - expressing cell lines.
 
Contributor(s) Kosno M, Currie SL, Kumar A, Xing C, Rosen MK
Citation(s) 37488172
Submission date May 24, 2023
Last update date Aug 23, 2023
Contact name Michael K Rosen
E-mail(s) michael.rosen@utsouthwestern.edu
Organization name UT Southwestern Medical Center
Department Biophysics
Lab Michael Rosen Laboratory
Street address 6001 Forest Park Rd., ND8.124
City Dallas
State/province TX
ZIP/Postal code 75235
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (14)
GSM7421832 HEK293 T-Rex Flp-In cells, BRD4-NUT, input
GSM7421833 HEK293 T-Rex Flp-In cells, BRD4-NUT, NUT antibody, biol rep 1
GSM7421834 HEK293 T-Rex Flp-In cells, BRD4-NUT, NUT antibody, biol rep 2
This SubSeries is part of SuperSeries:
GSE233303 Molecular features driving condensate formation and gene expression by the BRD4-NUT fusion oncoprotein are overlapping but distinct
Relations
BioProject PRJNA975834

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Supplementary file Size Download File type/resource
GSE233301_RAW.tar 50.6 Mb (http)(custom) TAR (of BROADPEAK, GAPPEDPEAK, NARROWPEAK)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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