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Series GSE75634 Query DataSets for GSE75634
Status Public on Jan 07, 2016
Title Invariant TAD boundaries constrain cell type-specific looping interactions between promoters and distal elements around the CFTR locus.
Organism Homo sapiens
Experiment type Other
Summary Three-dimensional genome structure plays an important role in gene regulation. Globally chromosomes are organized into active and inactive compartments, while at the gene level looping interactions connect promoters to regulatory elements. Topologically Associating Domains (TADs), typically several hundred kilobases in size form an intermediate level of organization. Major questions include how TADs are formed and what their relation is with looping interactions between genes and regulatory elements. Here we performed a focused 5C analysis of a 2.8 Mb region on chromosome 7 surrounding CFTR in a panel of cell types. We find that the same TAD boundaries are present in all cell types, indicating that TADs represent a universal chromosome architecture. Further, we find that these TAD boundaries are present irrespective of expression and looping of genes located between them. In contrast looping interactions between promoters and regulatory elements are cell-type specific and occur mostly within TADs. This is exemplified by the CFTR promoter that in different cell types interacts with distinct sets of distal cell type-specific regulatory elements that are all located within the same TAD. Finally, we find that long-range associations between loci located in different TADs are also detected but these display much lower interaction frequencies than looping interactions within TADs. Interestingly, interactions between TADs are also highly cell type-specific and often involve loci clustered around TAD boundaries. These data point to key roles of invariant TAD boundaries in constraining as well as mediating cell type-specific long-range interactions and gene regulation.
Overall design We investigated a 2.8 Mb region on Chromosome 7 (hg18 chr7: 115797757-118405450) containing the ENCODE region ENm001 42. The 5C experiment was designed to interrogate looping interactions between HindIII fragments containing transcription start sites (TSSs) and any other HindIII restriction fragment (distal fragments) in the target region. Libraries were generated for five cell lines: Caco2, Calu3, Capan1, GM12878 and HepG2, with two biological replicates for each line. 5C probes were designed at HindIII restriction sites (AAGCTT) using 5C primer design tools previously developed and made publicly available online at our My5C website ( Probes were designed based on the ENCODE manual region 1 (ENM001) design 25 with additional probes placed throughout the region when appropriate. We also added probes to extend the analysis to include a 700 Kb gene desert region located directly adjacent to ENM001. Probe settings were: U-BLAST, 3; S-BLAST, 100; 15-MER, 3,000; MIN_FSIZE, 250; MAX_FSIZE, 20,000; OPT_TM, 65; OPT_PSIZE, 40. We designed 74 reverse 5C probes, and 605 forward 5C probes.
Contributor(s) Smith EM, Lajoie BR, Jain G, Dekker J
Citation(s) 26748519
Submission date Dec 02, 2015
Last update date Jul 29, 2019
Contact name Bryan R Lajoie
Organization name UMMS
Department Program in Systems Biology
Lab Dekker Lab
Street address 368 Plantation St.
City Worcester
State/province MA
ZIP/Postal code 01605
Country USA
Platforms (1)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
Samples (10)
GSM1960843 Caco2 5C Rep1
GSM1960844 Caco2 5C Rep2
GSM1960845 Calu3 5C Rep1
BioProject PRJNA304769
SRA SRP066924

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
GSE75634_ENM001CFTR-Caco2-AACPSRRNCC-HG18.all.peakInfo.txt.gz 1.9 Mb (ftp)(http) TXT
GSE75634_ENM001CFTR-Caco2-AACPSRRNCC-HG18.interTAD.peakInfo.txt.gz 1.1 Mb (ftp)(http) TXT
GSE75634_ENM001CFTR-Caco2-AACPSRRNCC-HG18.intraTAD.peakInfo.txt.gz 725.0 Kb (ftp)(http) TXT
GSE75634_ENM001CFTR-Calu3-AACPSRRNCC-HG18.all.peakInfo.txt.gz 4.0 Mb (ftp)(http) TXT
GSE75634_ENM001CFTR-Calu3-AACPSRRNCC-HG18.interTAD.peakInfo.txt.gz 3.0 Mb (ftp)(http) TXT
GSE75634_ENM001CFTR-Calu3-AACPSRRNCC-HG18.intraTAD.peakInfo.txt.gz 891.1 Kb (ftp)(http) TXT
GSE75634_ENM001CFTR-Capan1-AACPSRRNCC-HG18.all.peakInfo.txt.gz 4.3 Mb (ftp)(http) TXT
GSE75634_ENM001CFTR-Capan1-AACPSRRNCC-HG18.interTAD.peakInfo.txt.gz 3.3 Mb (ftp)(http) TXT
GSE75634_ENM001CFTR-Capan1-AACPSRRNCC-HG18.intraTAD.peakInfo.txt.gz 890.9 Kb (ftp)(http) TXT
GSE75634_ENM001CFTR-GM12878-AACPSRRNCC-HG18.all.peakInfo.txt.gz 4.4 Mb (ftp)(http) TXT
GSE75634_ENM001CFTR-GM12878-AACPSRRNCC-HG18.interTAD.peakInfo.txt.gz 3.5 Mb (ftp)(http) TXT
GSE75634_ENM001CFTR-GM12878-AACPSRRNCC-HG18.intraTAD.peakInfo.txt.gz 881.1 Kb (ftp)(http) TXT
GSE75634_ENM001CFTR-HepG2-AACPSRRNCC-HG18.all.peakInfo.txt.gz 4.2 Mb (ftp)(http) TXT
GSE75634_ENM001CFTR-HepG2-AACPSRRNCC-HG18.interTAD.peakInfo.txt.gz 3.3 Mb (ftp)(http) TXT
GSE75634_ENM001CFTR-HepG2-AACPSRRNCC-HG18.intraTAD.peakInfo.txt.gz 873.5 Kb (ftp)(http) TXT
GSE75634_RAW.tar 3.0 Mb (http)(custom) TAR (of MATRIX, PNG) 688.4 Kb (ftp)(http) ZIP
GSE75634_tads_caco2.tar.gz 560.0 Kb (ftp)(http) TAR
GSE75634_tads_calu3.tar.gz 530.0 Kb (ftp)(http) TAR
GSE75634_tads_capan1.tar.gz 540.0 Kb (ftp)(http) TAR
GSE75634_tads_gm12878.tar.gz 530.0 Kb (ftp)(http) TAR
GSE75634_tads_hepg2.tar.gz 530.0 Kb (ftp)(http) TAR
GSE75634_tads_pooled-samples.tar.gz 270.0 Kb (ftp)(http) TAR
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