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Series GSE133163 Query DataSets for GSE133163
Status Public on Apr 01, 2020
Title Hi-C to Identify Interactions between Distant Genomic Loci due to BRD4-NUT-mediated Megadomain Formation
Organism Homo sapiens
Experiment type Other
Summary Delineating how chromosomes fold at length scales beyond one megabase remains obscure relative to smaller-scale folding into TADs, loops, and nucleosomes. We find that rather than simply unfolding chromatin, histone hyperacetylation results in interactions between distant genomic loci separated by tens to hundreds of megabases, even in the absence of transcription. These hyperacetylated “megadomains” are formed by the BRD4-NUT fusion oncoprotein, interact both within and between chromosomes, and form a specific nuclear subcompartment that has elevated gene activity with respect to other subcompartments. Pharmacological degradation of BRD4-NUT results in collapse of megadomains and attenuation of the interactions between them. In contrast, these interactions persist and contacts between newly acetylated regions are formed after inhibiting RNA polymerase II initiation. Our structure-function approach thus reveals that broad chromatin domains of identical biochemical composition, independent of transcription, form nuclear subcompartments, and also indicates the potential of altering chromosome structure
for treating human disease.
Overall design in situ Hi-C experiments mapping chromosome contacts after induction of BRD4-NUT expression in 293TRex cells and after MZ1 treatment to degrade BRD4-NUT, after MZ1 treatment followed by drug washout to partially restore BRD4-NUT protein levels, and after triptolide treatment to inhibit RNA polymerase II transcription in TC-797 cells.
Contributor(s) Eagen KP
Citation(s) 32243828
NIH grant(s)
Grant ID Grant title Affiliation Name
DP5 OD024587 Biochemical Basis of Chromatin Folding and Chromosome Condensation NORTHWESTERN UNIVERSITY AT CHICAGO Kyle Patrick Eagen
Submission date Jun 21, 2019
Last update date Jul 01, 2020
Contact name Kyle Eagen
Organization name Baylor College of Medicine
Department Department of Molecular and Cellular Biology
Lab Eagen Lab
Street address 1 Baylor Plaza
City Houston
State/province TX
ZIP/Postal code 77030
Country USA
Platforms (3)
GPL15520 Illumina MiSeq (Homo sapiens)
GPL20795 HiSeq X Ten (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (32)
GSM3901269 293TRex_uninduced_replicate1 (HiC)
GSM3901270 293TRex_uninduced_replicate2 (HiC)
GSM3901271 293TRex_induced_replicate1 (HiC)
This SubSeries is part of SuperSeries:
GSE133165 Chromatin Hyperacetylation Impacts Chromosome Folding by Forming a Nuclear Subcompartment
BioProject PRJNA550128
SRA SRP202551

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE133163_293trex_induced_combined.hic 4.2 Gb (ftp)(http) HIC
GSE133163_293trex_uninduced_TADs.bedpe.gz 427.7 Kb (ftp)(http) BEDPE
GSE133163_293trex_uninduced_combined.hic 4.0 Gb (ftp)(http) HIC
GSE133163_293trex_uninduced_loops.bedpe.gz 490.7 Kb (ftp)(http) BEDPE
GSE133163_RAW.tar 37.5 Gb (http)(custom) TAR (of HIC) 6.3 Mb (ftp)(http) TAR
GSE133163_tc-797_DMSO_TADs.bedpe.gz 513.8 Kb (ftp)(http) BEDPE
GSE133163_tc-797_DMSO_combined.hic 20.9 Gb (ftp)(http) HIC 437.1 Kb (ftp)(http) BW
GSE133163_tc-797_DMSO_loops.bedpe.gz 516.2 Kb (ftp)(http) BEDPE
GSE133163_tc-797_DMSO_mega-mega.bedpe.gz 93.7 Kb (ftp)(http) BEDPE 444.5 Kb (ftp)(http) BW 444.6 Kb (ftp)(http) BW 444.1 Kb (ftp)(http) BW 444.8 Kb (ftp)(http) BW 444.5 Kb (ftp)(http) BW 446.5 Kb (ftp)(http) BW
GSE133163_tc-797_DMSO_subcompartments.bed.gz 19.1 Kb (ftp)(http) BED
GSE133163_tc-797_MZ1_combined.hic 2.7 Gb (ftp)(http) HIC 437.6 Kb (ftp)(http) BW
GSE133163_tc-797_MZ1_mega-mega.bedpe.gz 2.5 Kb (ftp)(http) BEDPE
GSE133163_tc-797_triptolide_combined.hic 4.6 Gb (ftp)(http) HIC 447.8 Kb (ftp)(http) BW
GSE133163_tc-797_washout_combined.hic 3.3 Gb (ftp)(http) HIC 437.0 Kb (ftp)(http) BW
GSE133163_tc-797_washout_mega-mega.bedpe.gz 9.1 Kb (ftp)(http) BEDPE
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