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| Status |
Public on Jan 10, 2023 |
| Title |
Chromatin accessibility analysis of inducible HOTAIR overexpression mouse breast cancer cells |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
HOTAIR is a 2.2 kb long noncoding RNA (lncRNA) whose dysregulation has been linked to oncogenesis, defects in pattern formation during early development, and irregularities during the process of epithelial-to-mesenchymal transition (EMT). However, the oncogenic transformation determined by HOTAIR in vivo and its impact on chromatin dynamics are incompletely understood. Here we generate a transgenic mouse model with doxycycline-inducible expression of human HOTAIR in the context of the MMTV-PyMT breast cancer-prone background (iHOT-PyMT mice) to systematically interrogate the cellular mechanisms by which human HOTAIR lncRNA acts to promote breast cancer progression. We isolated breast cancer cells from the primary tumors of iHOT-PyMT mice (named iHOT+ cells) and performed RNA-seq and ATAC-seq of iHOT+ cells treated with 3 conditions: Dox+, Dox- and DoxWD. We showed that HOTAIR overexpression altered both the cellular transcriptome and chromatin accessibility landscape of multiple metastasis-associated genes and promoted epithelial to mesenchymal transition. These alterations are abrogated within several cell cycles after HOTAIR expression is reverted to basal levels, indicating an erasable lncRNA-associated epigenetic memory. These results suggest that a continual role for HOTAIR in programming a metastatic gene regulatory program.
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| Overall design |
The iHOT+ cells were treated with 3 conditions: Dox+ HOTAIR overexpressing cells which were consistently treated with Dox for several days; DoxWD cells which had been temporarily treated with Dox and later withdrawn from HOTAIR overexpression; and Dox- untreated control cells in which HOTAIR remained at baseline levels. Chromatin accessibility profiles in iHOT+ cells with different treatments were generated by ATAC-seq using the Illumina Genome Analyzer IIX platform.
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| Contributor(s) |
Ma Q, Tolentino K, Zhao Y, Li L |
| Citation(s) |
36579891 |
| Submission date |
Apr 26, 2022 |
| Last update date |
Jan 25, 2023 |
| Contact name |
Qing Ma |
| Organization name |
Shenzhen Institutes of Advanced Technology
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| Street address |
1068 Xueyuan Avenue, Shenzhen University Town, Shenzhen, P.R.China
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| City |
Shenzhen |
| ZIP/Postal code |
518055 |
| Country |
China |
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| Platforms (1) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE201873 |
Inducible lncRNA transgenic mice reveal continual role of HOTAIR in promoting breast cancer metastasis |
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| Relations |
| BioProject |
PRJNA832262 |
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