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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 [ATAC-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 |
ATAC-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 (4)
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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 |
PRJNA555878 |
SRA |
SRP215889 |
Supplementary file |
Size |
Download |
File type/resource |
GSE134619_RAW.tar |
428.8 Mb |
(http)(custom) |
TAR (of BIGWIG) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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