Metadata
- Name
- RNA expression changes in HOXA9/MEIS1 leukemia cells
- Repository
- Gene Expression Omnibus
- Identifier
- geo.series:GSE103447
- Description
- Aberrant expression of homeobox transcription factor HOXA9 is a central component of the leukemogenic program driven by diverse oncogenes. Here we show that HOXA9 overexpression in myeloid progenitor cells and pro-B cells leads to significant rearrangement of the epigenetic landscape with prominent emergence of cancer specific de novo enhancers. HOXA9 acts as a pioneer factor at the de novo enhancers and is required for recruitment of transcription factor CEBP/a and the histone H3K4 methyltransferase MLL3/MLL4 complex. HOXA9 function at the de novo enhancer is distinct from its physiological role at distal enhancers during normal hematopoietic development. Genetic deletion of MLL3/4 specifically affects the active enhancer signatures at de novo enhancers and inhibits HOXA9/MEIS1-mediated leukemogenesis. Our study reveals a previously uncharacterized role of HOXA9 and the MLL3/4 complex in leukemogenesis and provide mechanistic insights in epigenetic deregulation during malignant transformation.
- Data or Study Types
- Expression profiling by high throughput sequencing
- Source Organization
- National Center for Biotechnology Information
- Access Conditions
- available
- Year
- 2018
- Access Hyperlink
- http://www.ncbi.nlm.nih.gov/sites/GDSbrowser?acc=GSE103447
Distributions
- Encoding Format: TXT ; URL: ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE1nnn/GSE103447/matrix/
- Encoding Format: MINiML ; URL: ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE1nnn/GSE103447/miniml/
- Encoding Format: SOFT ; URL: ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE1nnn/GSE103447/soft/