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Series GSE93431 Query DataSets for GSE93431
Status Public on Jun 10, 2017
Title Two independent modes of chromosome organization are revealed by cohesin removal
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary The three-dimensional organization of chromosomes is tightly related to their biological function. Both imaging and chromosome conformation capture studies have revealed several layers of organization, including segregation into active and inactive compartments at the megabase scale, and partitioning into domains (TADs) and associated loops at the sub-megabase scale. Yet, it remains unclear how these layers of genome organization form, interact with one another, and contribute to or result from genome activities. TADs seem to have critical roles in regulating gene expression by promoting or preventing interactions between promoters and distant cis-acting regulatory elements, and different architectural proteins, including cohesin, have been proposed to play central roles in their formation. But so far, experimental depletions of these proteins have resulted in marginal changes in chromosome organization. Here, we show that deletion of the cohesin-loading factor, Nipbl, leads to loss of chromosome-associated cohesin and results in dramatic genome reorganization. TADs and associated loops vanish globally, even in the absence of transcriptional changes. In contrast, segregation into compartments is preserved and even reinforced. Strikingly, the disappearance of TADs unmasks a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrate that the 3D organization of the genome results from the independent action of two distinct mechanisms: 1) cohesin-independent segregation of the genome into fine-scale compartment regions, defined by the underlying chromatin state; and 2) cohesin-dependent formation of TADs possibly by the recently proposed loop extrusion mechanism, enabling long-range and target-specific activity of promiscuous enhancers. The interplay between these mechanisms creates an architecture that is more complex than a simple structural hierarchy and can be central to guiding normal development.
Overall design This submission contains the following experiments on primary hepatocytes isolated from wildtype (WT), control (TAM) and Nipbl-/- (NIPBL) mice: 2 biological replicates of Hi-C (TCC) in WT, TAM and NIPBL cells, 1 replicate of H3K27ac ChIP-seq in WT and NIPBL cells, 1 replicate of H3K4me3 ChIP-seq in WT and NIPBL cells, 1 replicate of Rad21 ChIP-seq in TAM and NIPBL cells, 1 replicate of Smc3 ChIP-seq in TAM and NIPBL cells, 1 replicate of CTCF ChIP-seq in TAM and NIPBL cells, 4 replicates of RNA-seq in each of WT, TAM and NIPBL cells.
Contributor(s) Schwarzer W, Abdennur N, Goloborodko A, Pekowska A, Fudenberg G, Loe-Mie Y, Fonseca NA, Huber W, Haering C, Mirny L, Spitz F
Citation(s) 29094699
Submission date Jan 11, 2017
Last update date May 15, 2019
Contact name Nezar Abdennur
Organization name MIT
Lab Mirny
Street address 77 Massachusetts Ave
City Cambridge
State/province MA
ZIP/Postal code 02139
Country USA
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (32)
GSM2453279 HiC-TCC_WT_Rep1
GSM2453280 HiC-TCC_WT_Rep2
GSM2453281 HiC-TCC_TAM_Rep1
BioProject PRJNA360958
SRA SRP096571

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 4.7 Mb (ftp)(http) HDF5 58.5 Mb (ftp)(http) HDF5 157.5 Mb (ftp)(http) HDF5 262.8 Mb (ftp)(http) HDF5 36.1 Mb (ftp)(http) HDF5 128.9 Mb (ftp)(http) HDF5 227.9 Mb (ftp)(http) HDF5 98.0 Mb (ftp)(http) HDF5 12.8 Mb (ftp)(http) HDF5 87.7 Mb (ftp)(http) HDF5 186.2 Mb (ftp)(http) HDF5 151.2 Mb (ftp)(http) BW 155.5 Mb (ftp)(http) BW
GSE93431_RAW.tar 5.4 Gb (http)(custom) TAR (of BW, HDF5, NARROWPEAK, TXT)
GSE93431_SummaryExpr_DEseq.csv.gz 1.1 Mb (ftp)(http) CSV 4.4 Mb (ftp)(http) HDF5 44.8 Mb (ftp)(http) HDF5 117.0 Mb (ftp)(http) HDF5 206.8 Mb (ftp)(http) HDF5 28.9 Mb (ftp)(http) HDF5 95.0 Mb (ftp)(http) HDF5 168.4 Mb (ftp)(http) HDF5 72.6 Mb (ftp)(http) HDF5 11.9 Mb (ftp)(http) HDF5 64.0 Mb (ftp)(http) HDF5 141.2 Mb (ftp)(http) HDF5 142.6 Mb (ftp)(http) BW 148.3 Mb (ftp)(http) BW 4.6 Mb (ftp)(http) HDF5 55.0 Mb (ftp)(http) HDF5 152.4 Mb (ftp)(http) HDF5 277.1 Mb (ftp)(http) HDF5 34.8 Mb (ftp)(http) HDF5 121.5 Mb (ftp)(http) HDF5 233.6 Mb (ftp)(http) HDF5 90.6 Mb (ftp)(http) HDF5 12.6 Mb (ftp)(http) HDF5 81.3 Mb (ftp)(http) HDF5 185.3 Mb (ftp)(http) HDF5 174.8 Mb (ftp)(http) BW 182.2 Mb (ftp)(http) BW
GSE93431_eigs.100kb.tsv.gz 906.7 Kb (ftp)(http) TSV
GSE93431_eigs.20kb.tsv.gz 4.4 Mb (ftp)(http) TSV
GSE93431_tads.lavaburst.corner.NIPBL.20kb.txt.gz 1.3 Mb (ftp)(http) TXT
GSE93431_tads.lavaburst.corner.UNTR.20kb.txt.gz 1001.0 Kb (ftp)(http) TXT
GSE93431_tads.lavaburst.modularity.NIPBL.20kb.txt.gz 698.9 Kb (ftp)(http) TXT
GSE93431_tads.lavaburst.modularity.UNTR.20kb.txt.gz 572.7 Kb (ftp)(http) TXT
GSE93431_tads.lavaburst.modularity.boundaryProbability.20kb.txt.gz 2.9 Mb (ftp)(http) TXT
Raw data are available in SRA
Processed data is available on Series record

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