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Series GSE172089 Query DataSets for GSE172089
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
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.
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.
Contributor(s) Rajderkar S, Zhu Y, Hu R, Li B, Zhang Y, Pennacchio L
Citation(s) 37081156
Submission date Apr 14, 2021
Last update date May 12, 2023
Contact name Sudha Rajderkar
Organization name Lawrence Berkeley National Laboratory
Street address 1 Cyclotron Rd
City Berkeley
State/province CA
ZIP/Postal code 94720
Country USA
Platforms (2)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (89)
GSM5241527 LocusB6_D2843
GSM5241528 LocusB6_D2851
GSM5241529 LocusB5_D2925
BioProject PRJNA721977
SRA SRP314851

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Supplementary file Size Download File type/resource
GSE172089_RAW.tar 104.7 Gb (http)(custom) TAR (of HIC, RESULTS)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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