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Status |
Public on Apr 22, 2021 |
Title |
The combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing
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Summary |
CTCF is a key organizer of the 3D genome. Its specialized paralog, BORIS, heterodimerizes with CTCF but is expressed only in male germ cells and in cancer states. Unexpectedly, BORIS-null mice have only minimal germ cell defects. To understand the CTCF-BORIS relationship, mouse models with varied CTCF and BORIS levels were generated. Whereas Ctcf+/+Boris+/+, Ctcf+/-Boris+/+, and Ctcf+/+Boris-/- males are fertile, Ctcf+/-Boris-/- (Compound Mutant; CM) males are sterile. Testes with combined depletion of both CTCF and BORIS show reduced size, defective meiotic recombination, increased apoptosis, and malformed spermatozoa. Although CM germ cells exhibit only 25% of CTCF WT expression, chromatin binding of CTCF is preferentially lost from CTCF-BORIS heterodimeric sites. Furthermore, CM testes lose the expression of a large number of spermatogenesis genes and gain the expression of developmentally inappropriate genes that are “toxic” to fertility. Thus, a combined action of CTCF and BORIS is required to both repress pre-meiotic genes and activate post-meiotic genes for a complete spermatogenesis program.
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Overall design |
Genome-wide mapping of CTCF and BORIS sites and mRNA expression profiles in Ctcf (+/+)Boris(+/+), Ctcf (+/-)Boris(+/+), Ctcf +/+Boris(-/-), and Ctcf (+/-)Boris(-/-) [also called 'DKO' or 'CM'] mouse whole testes, round spermatids , and spermatocytes
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Contributor(s) |
Rivero-Hinojosa S, Pugacheva E, Lobanenkov V |
Citation(s) |
34158481 |
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Submission date |
Jul 11, 2020 |
Last update date |
Jun 23, 2021 |
Contact name |
Samuel Rivero-Hinojosa |
E-mail(s) |
sriverohin@childrensnational.org
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Phone |
2024765801
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Organization name |
Children’s National Health System
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Department |
Children’s Research Institute, Center for Cancer and Immunology Research
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Street address |
111 Michigan Ave NW
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City |
Washington |
State/province |
District of Columbia |
ZIP/Postal code |
20010 |
Country |
USA |
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Platforms (3) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
GPL18635 |
Ion Torrent Proton (Mus musculus) |
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Samples (54)
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Relations |
BioProject |
PRJNA645574 |
SRA |
SRP271386 |
Supplementary file |
Size |
Download |
File type/resource |
GSE154249_DKO_CTCF_ChIP-seq.wig.gz |
583.5 Mb |
(ftp)(http) |
WIG |
GSE154249_DKO_CTCF_ChIP-seq_peaks.bed.gz |
297.3 Kb |
(ftp)(http) |
BED |
GSE154249_DKO_H3K4me3_ChIP-seq.wig.gz |
442.7 Mb |
(ftp)(http) |
WIG |
GSE154249_DKO_H3K4me3_ChIP-seq_peaks.bed.gz |
301.4 Kb |
(ftp)(http) |
BED |
GSE154249_DKO_Pol2_ChIP-seq.wig.gz |
549.3 Mb |
(ftp)(http) |
WIG |
GSE154249_DKO_Pol2_ChIP-seq_peaks.bed.gz |
409.6 Kb |
(ftp)(http) |
BED |
GSE154249_RS_and_SC_raw_counts_matrix.txt.gz |
843.3 Kb |
(ftp)(http) |
TXT |
GSE154249_WT_BORIS_ChIP-seq.wig.gz |
469.2 Mb |
(ftp)(http) |
WIG |
GSE154249_WT_BORIS_ChIP-seq_peaks.bed.gz |
105.5 Kb |
(ftp)(http) |
BED |
GSE154249_WT_CTCF_ChIP-seq.wig.gz |
542.7 Mb |
(ftp)(http) |
WIG |
GSE154249_WT_CTCF_ChIP-seq_peaks.bed.gz |
487.5 Kb |
(ftp)(http) |
BED |
GSE154249_WT_H3K4me3_ChIP-seq.wig.gz |
258.2 Mb |
(ftp)(http) |
WIG |
GSE154249_WT_H3K4me3_ChIP-seq_peaks.bed.gz |
490.0 Kb |
(ftp)(http) |
BED |
GSE154249_WT_Pol2_ChIP-seq.wig.gz |
570.4 Mb |
(ftp)(http) |
WIG |
GSE154249_WT_Pol2_ChIP-seq_peaks.bed.gz |
365.9 Kb |
(ftp)(http) |
BED |
GSE154249_Whole_testis_raw_counts_matrix.txt.gz |
459.6 Kb |
(ftp)(http) |
TXT |
GSE154249_koSC_CTCF_ChIP_Rep1_control_lambda.bedgraph.gz |
273.5 Mb |
(ftp)(http) |
BEDGRAPH |
GSE154249_koSC_CTCF_ChIP_Rep1_treat_pileup.bedgraph.gz |
159.0 Mb |
(ftp)(http) |
BEDGRAPH |
GSE154249_koSC_CTCF_ChIP_Rep2_treat_pileup.bedgraph.gz |
161.7 Mb |
(ftp)(http) |
BEDGRAPH |
GSE154249_wtSC_CTCF_ChIP_treat_afterfiting_all.wig.gz |
273.4 Mb |
(ftp)(http) |
WIG |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |