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Updated: Feb 28, 2026
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Genome-wide Analysis using ChIP to Identify Isoform-specific Gene Targets
Published on: July 7, 2010
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PHF6 regulates phenotypic plasticity through chromatin organization within lineage-specific genes
Yadira M Soto-Feliciano1,2, Jordan M E Bartlebaugh1,2, Yunpeng Liu1,2
1David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
Genes & Development
|June 14, 2017
Summary
Loss of plant homeodomain finger protein 6 (PHF6) in leukemia alters chromatin accessibility, promoting lineage plasticity. This change impacts gene expression, leading to altered disease presentation and therapy response.
Area of Science:
- Molecular Biology
- Hematology
- Cancer Biology
Background:
- Lineage plasticity in malignancies contributes to tumor progression and drug resistance.
- The molecular mechanisms underlying this plasticity remain largely unknown.
Purpose of the Study:
- To investigate the role of plant homeodomain finger protein 6 (PHF6) in leukemia.
- To define PHF6's function in regulating chromatin accessibility for lineage-specific transcription factors.
Main Methods:
- Studied the impact of PHF6 loss (Phf6 knockout) in B-cell leukemia models.
- Analyzed changes in gene expression and chromatin landscape.
- Assessed in vivo tumor development and lineage plasticity.
Main Results:
- Loss of PHF6 alters chromatin accessibility at transcriptional start sites.
- Down-regulation of B-cell development genes and up-regulation of T-cell signaling genes observed in Phf6 knockout cells.
- Phf6 knockout cells developed mixed-lineage lymphoma in vivo, exhibiting phenotypic plasticity.
Conclusions:
- PHF6 is crucial for maintaining leukemia cell identity by regulating the chromatin landscape.
- Loss of PHF6 induces focal changes in chromatin accessibility, enabling lineage transition.
- This plasticity affects disease presentation, oncogenic signaling tolerance, and therapeutic sensitivity.
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