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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 24, 2020 |
| Title |
TOPORS, a tumor suppressor protein, maintains higher-order chromatin organization in mouse hepatocytes [PML ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Within mammalian nuclear space, chromosomes are hierarchically folded into active (A) and inactive (B) compartments composed of topologically associating domains (TADs). Genomic regions interact with nuclear lamina, termed lamina-associated domains (LADs), associated with transcriptional repression. However, the molecular mechanisms underlying these 3D chromatin architectures remain undeciphered. Here, we demonstrate the role of a potential tumor suppressor, TOP1 Binding Arginine/Serine Rich Protein (TOPORS), in genome organization. Topors knockdown in mouse hepatocytes results in cell proliferation and migration promotion, as well as arrest in the S phase of the cell cycle. RNA-seq analysis shows that 373 genes are up-regulated, some of which are associated with nuclear structure, and 316 genes exhibit down-regulated, many related to metabolic process. Chromatin accessibility is inclined to alter in the intergenic regions, including enhancers. Chromatin-lamina interactions decrease globally, and the coverage of LADs reduces from 53.31% to 46.52%. Furthermore, Topors knockdown leads to significantly increasing interactions between A and B compartments in cis and in trans. Correspondingly, strength of TAD boundaries located at A/B borders is weakened. Collectively, our data reveal that TOPORS functions as a regulator in chromosome folding, providing novel insights into the architectural role of tumor suppressors in higher-order genome organization.
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| Overall design |
PML ChIP-seq data in Ctrl and Topors KD AML12 cells.
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| Citation(s) |
32113985 |
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| Submission date |
Jul 22, 2019 |
| Last update date |
Sep 25, 2020 |
| Contact name |
Bo Wen |
| E-mail(s) |
bowen75@fudan.edu.cn
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| Organization name |
Fudan University
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| Street address |
130 Dongan Rd.
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| City |
ShangHai |
| ZIP/Postal code |
200032 |
| Country |
China |
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| Platforms (1) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE134624 |
TOPORS, a tumor suppressor protein, maintains higher-order chromatin organization in mouse hepatocytes |
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| Relations |
| BioProject |
PRJNA555875 |
| SRA |
SRP215875 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE134622_RAW.tar |
1.3 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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