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Metadata

Name
Transcription Factor MEF2D is Required for the Maintenance of MLL-rearranged Acute Myeloid Leukemia [ChIP-Seq]
Repository
Gene Expression Omnibus
Identifier
geo.series:GSE165980
Description
Acute myeloid leukemia (AML) with MLL-rearrangement (MLL-r) comprises approximately 10% of all AML cases and portends poor outcomes. Much remains to be uncovered on how MLL-r AML drives leukemia development while preventing cells from normal myeloid differentiation. Here, we identified that transcription factor MEF2D is a highly expressed gene with a super-enhancer MLL-r AML. Knockout of MEF2D profoundly impaired leukemia growth, induced myeloid differentiation, and delayed oncogenic progression in vivo. Mechanistically, MEF2D loss led to robust activation of a CEBPE-centered myeloid differentiation program in AML cells. Chromatin profiling revealed that MEF2D binds to and suppresses the chromatin accessibility of CEBPE cis-regulatory regions. In human acute leukemia patient samples, MEF2D expression showed a strong negative correlation with the expression of CEBPE. Depletion of CEBPE partially rescued the cell growth defect and myeloid cell differentiation induced by the loss of MEF2D. Lastly, we show that MEF2D is positively regulated by HOXA9, and downregulation of MEF2D is an important mechanism for DOT1L inhibitor-induced anti-leukemia effects in MLL-r AML. Collectively, our findings suggest that MEF2D plays a critical role in human MLL-r AML and uncover the MEF2D-CEBPE axis as a crucial transcriptional mechanism regulating leukemia cell self-renewal and differentiation block in MLL-r AML.
Data or Study Types
Genome binding/occupancy profiling by high throughput sequencing
Source Organization
National Center for Biotechnology Information
Access Conditions
available
Year
2021
Access Hyperlink
http://www.ncbi.nlm.nih.gov/sites/GDSbrowser?acc=GSE165980

Distributions

  • Encoding Format: TXT ; URL: ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE1nnn/GSE165980/matrix/
  • Encoding Format: MINiML ; URL: ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE1nnn/GSE165980/miniml/
  • Encoding Format: SOFT ; URL: ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE1nnn/GSE165980/soft/
This project was funded in part by grant U24AI117966 from the NIH National Institute of Allergy and Infectious Diseases as part of the Big Data to Knowledge program. We thank all members of the bioCADDIE community for their valuable input on the overall project.