|
| Status |
Public on Oct 20, 2023 |
| Title |
TAD Evolutionary and functional characterization reveals diversity in mammalian TAD boundary properties and function |
| Organisms |
Macaca mulatta; Homo sapiens; Mus caroli; Mus musculus; Mus pahari; Rattus norvegicus; Nomascus leucogenys; Hylobates moloch |
| Experiment type |
Other
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
|
| Summary |
Topological associating domains (TADs) are self-interacting genomic units crucial for shaping gene regulation patterns. Despite their importance, the extent of their evolutionary conservation and its functional implications remain largely unknown. In this study, we generate Hi-C and ChIP-seq data and compare TAD organization across four primate and four rodent species, and characterize the genetic and epigenetic properties of TAD boundaries in correspondence to their evolutionary conservation. We find 14% of all human TAD boundaries to be shared among all eight species (ultraconserved), while 15% are human-specific. Ultraconserved TAD boundaries have stronger insulation strength, CTCF binding, and enrichment of older retrotransposons, compared to species-specific boundaries. CRISPR-Cas9 knockouts of two ultraconserved boundaries in mouse models leads to tissue-specific gene expression changes and morphological phenotypes. Deletion of a human-specific boundary near the autism-related AUTS2 gene results in upregulation of this gene in neurons. Overall, our study provides pertinent TAD boundary evolutionary conservation annotations, and showcase the functional importance of TAD evolution.
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| Overall design |
We sequenced H3K4me3, H3K27me3, H3K4me1, H3K27ac, and CTCF ChIP-seq of three rodent species liver tissue, and LCL from two gibbon species. A Male and female biological replicate were sequenced for each mark and species. To test functionality of human-specific boundaries, we used CRISPR to knock-out a human-specific TAD boundary (two replicated) in iPSC-induced neurons, and used HiC to compare chromatin interaction between wild-type (two replicated) and knock-out cells. To test functionality of ultraconserved boundaries, we used CRISPR to knock-out a candidate ultra-conserved TAD boundaries in mouse, and used Capture HiC to compare chromatin interaction in the heart of wild-type (two replicates) and knock-out mice (two replicates).
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| Contributor(s) |
Okhovat M, VanCampen J, Carbone L |
| Citation(s) |
38062027 |
| Submission date |
Mar 04, 2022 |
| Last update date |
Dec 14, 2023 |
| Contact name |
Mariam Okhovat |
| Organization name |
Oregon Health and Science University
|
| Department |
Medicine
|
| Street address |
3030 S Moody Ave.
|
| City |
Portland |
| State/province |
Oregon |
| ZIP/Postal code |
97239 |
| Country |
USA |
| |
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| Platforms (9)
|
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
| GPL22396 |
Illumina HiSeq 4000 (Rattus norvegicus) |
| GPL23949 |
Illumina HiSeq 4000 (Macaca mulatta) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
| GPL27430 |
Illumina HiSeq 4000 (Nomascus leucogenys) |
| GPL32021 |
Illumina HiSeq 4000 (Hylobates moloch) |
| GPL32022 |
Illumina HiSeq 4000 (Mus caroli) |
| GPL32023 |
Illumina HiSeq 4000 (Mus pahari) |
|
| Samples (85)
|
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| Relations |
| BioProject |
PRJNA812880 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE197926_AUTS2_min10_max60_fdr01_d01_score.bedgraph.gz |
3.1 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE197926_B14804_HiC.xlsx |
95.9 Kb |
(ftp)(http) |
XLSX |
| GSE197926_B396+B5234_Capture-HiC.xlsx |
97.2 Kb |
(ftp)(http) |
XLSX |
| GSE197926_B396.BOS_RNA-seq.xlsx |
97.0 Kb |
(ftp)(http) |
XLSX |
| GSE197926_HMO-gibbon-CTCF-peaks-combined-merge200bp-sorted.bed.gz |
380.5 Kb |
(ftp)(http) |
BED |
| GSE197926_HMO-gibbon-CTCF.bigwig |
425.1 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_HMO-gibbon-H3K27ac.bigwig |
417.9 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_HMO-gibbon-H3K27me3.bigwig |
537.5 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_HMO-gibbon-H3K4me1.bigwig |
471.1 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_HMO-gibbon-H3K4me3.bigwig |
238.5 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_HMO-gibbon-input.bigwig |
415.1 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_HOM.cool.gz |
4.1 Mb |
(ftp)(http) |
COOL |
| GSE197926_HOM_min10_max60_fdr_d01_score.bedgraph.gz |
2.6 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE197926_NLE-gibbon-CTCF-peaks-combined-merge200bp-sorted.bed.gz |
322.1 Kb |
(ftp)(http) |
BED |
| GSE197926_NLE-gibbon-CTCF.bigwig |
315.4 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_WT.cool.gz |
3.8 Mb |
(ftp)(http) |
COOL |
| GSE197926_WT_min10_max60_fdr01_d01_score.bedgraph.gz |
3.1 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE197926_WT_min10_max60_fdr_d01_score.bedgraph.gz |
2.6 Mb |
(ftp)(http) |
BEDGRAPH |
| GSE197926_caroli-CTCF-peaks-combined-merge200bp-sorted.bed.gz |
349.0 Kb |
(ftp)(http) |
BED |
| GSE197926_caroli-CTCF.bigwig |
475.9 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_caroli-H3K27ac.bigwig |
360.6 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_caroli-H3K27me3.bigwig |
419.8 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_caroli-H3K4me1.bigwig |
430.0 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_caroli-H3K4me3.bigwig |
395.2 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_hMol2_HiC_min10_max60_fdr01_d01_boundaries.bed.gz |
120.5 Kb |
(ftp)(http) |
BED |
| GSE197926_mCar1_HiC_min10_max60_fdr01_d01_boundaries.bed.gz |
121.3 Kb |
(ftp)(http) |
BED |
| GSE197926_mPah1_HiC_min10_max60_fdr01_d01_boundaries.bed.gz |
112.5 Kb |
(ftp)(http) |
BED |
| GSE197926_merged-rat-CTCF-ChIP-bowtie2-30qual-filter_FE.sorted.bw |
1.6 Gb |
(ftp)(http) |
BW |
| GSE197926_merged-rat-H3K27ac-ChIP-bowtie2-30qual-filter_FE.sorted.bw |
1.4 Gb |
(ftp)(http) |
BW |
| GSE197926_merged-rat-H3K27me3-ChIP-bowtie2-30qual-filter_FE.sorted.bw |
1.3 Gb |
(ftp)(http) |
BW |
| GSE197926_merged-rat-H3K4me1-ChIP-bowtie2-30qual-filter_FE.sorted.bw |
1.4 Gb |
(ftp)(http) |
BW |
| GSE197926_merged-rat-H3K4me3-ChIP-bowtie2-30qual-filter_FE.sorted.bw |
1.5 Gb |
(ftp)(http) |
BW |
| GSE197926_mm10_HiC_min10_max60_fdr01_d01_boundaries.bed.gz |
110.6 Kb |
(ftp)(http) |
BED |
| GSE197926_mouse-CTCF-peaks-combined-merge200bp-sorted.bed.gz |
533.9 Kb |
(ftp)(http) |
BED |
| GSE197926_mouse-CTCF.bigwig |
454.6 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_mouse-H3K27ac.bigwig |
364.3 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_mouse-H3K27me3.bigwig |
446.1 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_mouse-H3K4me1.bigwig |
335.4 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_mouse-H3K4me3.bigwig |
420.2 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_mouse-liver-8-chromatin-states.bed.gz |
2.8 Mb |
(ftp)(http) |
BED |
| GSE197926_nomLeu4_HiC_min10_max60_fdr01_d01_boundaries.bed.gz |
116.4 Kb |
(ftp)(http) |
BED |
| GSE197926_pahari-CTCF-peaks-combined-merge200bp-sorted.bed.gz |
390.9 Kb |
(ftp)(http) |
BED |
| GSE197926_pahari-CTCF.bigwig |
325.2 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_pahari-H3K27ac.bigwig |
313.9 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_pahari-H3K27me3.bigwig |
382.3 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_pahari-H3K4me1.bigwig |
397.1 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_pahari-H3K4me3.bigwig |
265.9 Mb |
(ftp)(http) |
BIGWIG |
| GSE197926_rat-CTCF-peaks-combined-merge200bp-sorted.bed.gz |
529.7 Kb |
(ftp)(http) |
BED |
| GSE197926_rheMac10_HiC_min10_max60_fdr01_d01_boundaries.bed.gz |
131.2 Kb |
(ftp)(http) |
BED |
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