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| Status |
Public on Apr 17, 2023 |
| Title |
Topologically Associating Domain Boundaries are Required for Normal Genome Function |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Large-scale reaarangements and/or disruption of the three dimensional organization of the mammalian genome has been shown to cause develomental phenotypes. However, the functional requirement of TAD boundaries alone in development and disease remains an outstanding question in the field. Here, we show that TAD boundaries are required for the functional integrity of the genome in vivo. Using systematic genome-wide selection criteria and CRISPR/Cas9 editing, we deleted eight individual TAD boundaries ranging between 11-80 kb in size and investigated the in vivo consequences comprehensively by assessing survival, chromatin interaction data, gene expression and detailed phenotypic characterization. A majority of boundary deletions resulted in altered chromatin interactions, and/or multiple boundary deletions causing reduced embryonic survival or other developmental phenotypes. Our results elucidate the functional requirement of TAD boundary integrity in development and suggest that TAD bondary deletion may be sufficient to cause developmental phenotypes.
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| Overall design |
For chromosome conformation capture (HiC), liver tissue from TAD boundary mutant and wild type control mice, at age p56, was collected, processed and analyzed for HiC per standard protocols. RNA-seq was performed using standard protocols on the indicated tissue from E11.5 embryos, homozygous as well as wild type controls, for each of the TAD boundary deletion lines.
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| Contributor(s) |
Rajderkar S, Zhu Y, Hu R, Li B, Zhang Y, Pennacchio L |
| Citation(s) |
37081156 |
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| Submission date |
Apr 14, 2021 |
| Last update date |
May 12, 2023 |
| Contact name |
Sudha Rajderkar |
| E-mail(s) |
rajderkarsudha@gmail.com
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| Organization name |
Lawrence Berkeley National Laboratory
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| Street address |
1 Cyclotron Rd
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| City |
Berkeley |
| State/province |
CA |
| ZIP/Postal code |
94720 |
| Country |
USA |
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| Platforms (2) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (89)
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| Relations |
| BioProject |
PRJNA721977 |
| SRA |
SRP314851 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE172089_RAW.tar |
104.7 Gb |
(http)(custom) |
TAR (of HIC, RESULTS) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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