Related Experiment Video
Updated: Feb 4, 2026
10:02
Identification of Enhancer-Promoter Contacts in Embryoid Bodies by Quantitative Chromosome Conformation Capture 4C
Published on: April 29, 2020
7.1K
HOXA9 Reprograms the Enhancer Landscape to Promote Leukemogenesis
Yuqing Sun1, Bo Zhou1, Fengbiao Mao1
1Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Cancer Cell
|October 2, 2018
Summary
Overexpression of HOXA9 in acute leukemia drives enhancer reorganization and activates embryonic genes. Targeting HOXA9-dependent enhancer changes offers a potential therapeutic strategy for this cancer.
Area of Science:
- Molecular Biology
- Cancer Biology
- Epigenetics
Background:
- Aberrant HOXA9 expression is a hallmark of acute leukemia.
- HOXA9 drives leukemogenesis through various oncogenic pathways.
Purpose of the Study:
- To investigate the role of HOXA9 in enhancer reorganization in acute leukemia.
- To elucidate the molecular mechanisms by which HOXA9 alters the enhancer landscape and gene expression.
Main Methods:
- Analysis of enhancer landscape changes in myeloid and B progenitor cells with HOXA9 overexpression.
- Chromatin immunoprecipitation (ChIP) assays to identify transcription factor binding and histone modifications.
- Genetic deletion of MLL3/MLL4 to assess their role in HOXA9-mediated leukemogenesis.
- In vivo leukemogenesis studies.
Main Results:
- HOXA9 overexpression induces significant enhancer reorganization, creating de novo enhancers specific to leukemia.
- These alterations activate an ectopic embryonic gene program.
- HOXA9 acts as a pioneer factor at de novo enhancers, recruiting CEBPα and the MLL3/MLL4 complex.
- Deletion of MLL3/MLL4 prevents histone H3K4 methylation at de novo enhancers and inhibits leukemogenesis.
Conclusions:
- HOXA9 orchestrates enhancer reorganization, leading to aberrant gene activation in acute leukemia.
- The MLL3/MLL4 complex is crucial for HOXA9-mediated enhancer function and leukemogenesis.
- Targeting HOXA9-driven enhancer alterations presents a promising therapeutic avenue for acute leukemia.
Related Concept Videos
02:40The Eukaryotic Promoter Region
18.8K
The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
18.8K
02:40The Eukaryotic Promoter Region
4.0K
4.0K
01:14Introduction to Nuclear Reprogramming
2.3K
Nuclear reprogramming is the process of switching gene expression of one cell type to that of another cell type, usually from a differentiated cell state to an undifferentiated cell state. Differentiation occurs during processes such as development and morphogenesis, tissue regeneration, and malignancy. Cells can also be artificially induced to reprogram their gene expression by techniques such as nuclear transfer, induced pluripotency, and cell fusion. Such techniques have many applications in...
2.3K
01:24Methods of Nuclear Reprogramming
2.1K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
2.1K
03:00Self-Evaluation: Self-Enhancement and Self-Verification
5.8K
Social psychologists have documented that feeling good about ourselves and maintaining positive self-esteem is a powerful motivator of human behavior (Tavris & Aronson, 2008). In the United States, members of the predominant culture typically think very highly of themselves and view themselves as good people who are above average on many desirable traits (Ehrlinger, Gilovich, & Ross, 2005). Often, our behavior, attitudes, and beliefs are affected when we experience a threat to our...
5.8K
00:50Anaphase Promoting Complex
3.5K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.5K