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GEO help: Mouse over screen elements for information. |
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Status |
Public on Mar 10, 2016 |
Title |
Identification of chromatin accessibility domains in EMT and breast cancer stem cell formation. |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Epithelial-mesenchymal transition (EMT), the process whereby cells gain migratory and invasive properties characteristic of mesenchymal cells, plays a central role in embryogenesis and wound healing in a wide range of tissues. However, EMT has also been linked to the formation of cancer stem cells (CSCs). Many of the signaling pathways involved in EMT have also been implicated in CSC formation but the processes that contribute uniquely to CSC formation remain elusive. We have previously demonstrated that PKCθ activation is critical for EMT induction and concomitant CSC formation in the breast cancer luminal epithelial cell line, MCF7. To discover how PKC-induced alterations in the epigenome influence the EMT and CSC formation in MCF-7 cells, we employed a combination of expression profiling and Formaldehyde Assisted Regulatory Elements (FAIRE)-sequencing in order to reveal novel links between gene expression and DNA accessibility changes after PKCθ activation. We found that, during EMT, increases in accessibility generally occurred in regions away from transcription start sites, low in CpG, enriched with chromatin marks of enhancer elements and motifs for FOX, AP1, TEAD and AP2. Increases in FOX and AP-1 motif accessibility were associated with genes that exhibited increased expression in CSC, while increased AP-2 accessibility was associated with genes that had higher expression in non-CSCs. This study revealed novel regions of DNA accessibility induced by PKC that contribute to the understanding of how epigenomic plasticity of cells undergoing EMT leads to the activation of genes that drive the CSC program.
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Overall design |
2 biological samples were analysed with 2 biological replicates each and a mixed total input.
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Contributor(s) |
Hardy K, Zafar A, Rao S |
Citation(s) |
26962893 |
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Submission date |
Jul 16, 2015 |
Last update date |
May 15, 2019 |
Contact name |
Kristine Hardy |
E-mail(s) |
kristine.hardy@anu.edu.au
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Organization name |
University of Canberra
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Lab |
Cytokine Gene Expression
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Street address |
University of Canberra
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City |
Bruce |
State/province |
ACT |
ZIP/Postal code |
0200 |
Country |
Australia |
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Platforms (1) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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Samples (5)
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Relations |
BioProject |
PRJNA290114 |
SRA |
SRP061249 |
Supplementary file |
Size |
Download |
File type/resource |
GSE71023_RAW.tar |
2.0 Gb |
(http)(custom) |
TAR (of BED, BEDGRAPH) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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