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Status |
Public on Jan 12, 2019 |
Title |
An alternative CTCF isoform antagonizes canonical CTCF occupancy and changes chromatin architecture to promote apoptosis |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing
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Summary |
CTCF plays key roles in gene regulation, chromatin insulation, imprinting, X chromosome inactivation and organizing the higher-order chromatin architecture of mammalian genomes. Previous studies have mainly focused on the roles of the canonical CTCF isoform. Here, we explore the functions of an alternatively spliced human CTCF isoform in which exons 3 and 4 are skipped, producing a shorter isoform (CTCF-s). Functionally, we find that CTCF-s competes with the genome binding of canonical CTCF and binds a similar DNA sequence. CTCF-s binding disrupts CTCF/cohesin binding, alters CTCF-mediated chromatin looping and promotes the activation of IFI6 that leads to apoptosis. This effect is caused by an abnormal long-range interaction at the IFI6 enhancer and promoter. Taken together, this study reveals a non-canonical function for CTCF-s that antagonizes the genomic binding of canonical CTCF and cohesin, and that modulates chromatin looping and causes apoptosis by stimulating IFI6 expression.
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Overall design |
ChIP-seq of CTCF and CTCF-s and RNA-seq of Hela S3 cells with overexpression or knockdown of CTCF and CTCF-s. Also included are HiChIP-seq of control or CTCF-s overexpressing Hela S3 cells.
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Contributor(s) |
Huang K, Li J, Hu G, Yao H |
Citation(s) |
30948729 |
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Submission date |
Jan 08, 2018 |
Last update date |
May 14, 2019 |
Contact name |
Kaimeng Huang |
E-mail(s) |
Kaimeng_huang@dfci.harvard.edu
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Organization name |
Dana-Farber Cancer Institute
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Street address |
4 Blackfan Circle
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City |
Boston |
State/province |
MA |
ZIP/Postal code |
02215 |
Country |
USA |
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Platforms (2) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
GPL20795 |
HiSeq X Ten (Homo sapiens) |
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Samples (30)
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Relations |
BioProject |
PRJNA428981 |
SRA |
SRP128556 |
Supplementary file |
Size |
Download |
File type/resource |
GSE108869_CTCF-s_OE_CTCF-HiChIP_combine_allValidPairs.hic |
3.7 Gb |
(ftp)(http) |
HIC |
GSE108869_CTCF-s_OE_CTCF_ChIPSeq.narrowPeak.gz |
2.0 Mb |
(ftp)(http) |
NARROWPEAK |
GSE108869_CTCF-s_OE_CTCF_ChIPSeq_control.bw |
916.5 Mb |
(ftp)(http) |
BW |
GSE108869_CTCF-s_OE_CTCF_ChIPSeq_treat.bw |
346.9 Mb |
(ftp)(http) |
BW |
GSE108869_CTCF-s_OE_RAD21_ChIPSeq_control_lambda.bw |
514.2 Mb |
(ftp)(http) |
BW |
GSE108869_CTCF-s_OE_RAD21_ChIPSeq_peaks.narrowPeak.gz |
1.4 Mb |
(ftp)(http) |
NARROWPEAK |
GSE108869_CTCF-s_OE_RAD21_ChIPSeq_treat_pileup.bw |
229.5 Mb |
(ftp)(http) |
BW |
GSE108869_CTCF_CTCF-s_OE_RNA-seq.tsv.gz |
250.3 Kb |
(ftp)(http) |
TSV |
GSE108869_Control_CTCF-HiChIP_combine_allValidPairs.hic |
3.1 Gb |
(ftp)(http) |
HIC |
GSE108869_Control_CTCF_ChIPSeq.narrowPeak.gz |
2.1 Mb |
(ftp)(http) |
NARROWPEAK |
GSE108869_Control_CTCF_ChIPSeq_control.bw |
846.4 Mb |
(ftp)(http) |
BW |
GSE108869_Control_CTCF_ChIPSeq_treat.bw |
354.7 Mb |
(ftp)(http) |
BW |
GSE108869_Control_RAD21_ChIPSeq_control_lambda.bw |
517.8 Mb |
(ftp)(http) |
BW |
GSE108869_Control_RAD21_ChIPSeq_peaks.narrowPeak.gz |
1.9 Mb |
(ftp)(http) |
NARROWPEAK |
GSE108869_Control_RAD21_ChIPSeq_treat_pileup.bw |
182.7 Mb |
(ftp)(http) |
BW |
GSE108869_FLAG-CTCF-s.narrowPeak.gz |
460.8 Kb |
(ftp)(http) |
NARROWPEAK |
GSE108869_FLAG-CTCF-s_control_lambda.bw |
487.8 Mb |
(ftp)(http) |
BW |
GSE108869_FLAG-CTCF-s_treat_pileup.bw |
244.0 Mb |
(ftp)(http) |
BW |
GSE108869_FLAG-CTCF.narrowPeak.gz |
395.5 Kb |
(ftp)(http) |
NARROWPEAK |
GSE108869_FLAG-CTCF_control_lambda.bw |
495.3 Mb |
(ftp)(http) |
BW |
GSE108869_FLAG-CTCF_treat_pileup.bw |
244.9 Mb |
(ftp)(http) |
BW |
GSE108869_Knockdown_RNA-seq.tsv.gz |
310.9 Kb |
(ftp)(http) |
TSV |
GSE108869_biotin-CTCF-s_bioChIP_redup_with_SPMR_peaks.narrowPeak.gz |
978.3 Kb |
(ftp)(http) |
NARROWPEAK |
GSE108869_biotin-CTCF-s_sorted_control_lambda.bw |
370.5 Mb |
(ftp)(http) |
BW |
GSE108869_biotin-CTCF-s_treat_pileup.bw |
198.5 Mb |
(ftp)(http) |
BW |
GSE108869_biotin-CTCF_bioChIP_redup_with_SPMR_peaks.narrowPeak.gz |
1.9 Mb |
(ftp)(http) |
NARROWPEAK |
GSE108869_biotin-CTCF_sorted_control_lambda.bw |
369.9 Mb |
(ftp)(http) |
BW |
GSE108869_biotin-CTCF_treat_pileup.bw |
150.6 Mb |
(ftp)(http) |
BW |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |