HIRA-SETDB1-H3K9me3 axis regulates chromatin architecture in leukemia cells

Q: What does this research mean for the field?

Loss of HIRA in chronic myeloid leukemia cells promotes global chromatin condensation and restricts cell proliferation via the SETDB1-H3K9me3 axis, demonstrating that elevated HIRA expression is critical for CML pathogenesis and BCR-ABL expression. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Mayur Balkrishna Shirude; Anjali Devarajan; Sai Adarsh Sahu; Ananda Mukherjee; Debasree Dutta

doi:10.1016/j.jbc.2026.113081

April 1, 2026Journal of Biological ChemistryOpen Access

HIRA-SETDB1-H3K9me3 axis regulates chromatin architecture in leukemia cells

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Key Points

This study aims to uncover the mechanisms linking HIRA to chromatin reorganization and leukemia pathogenesis.
Developed a HIRA knockdown K562 CML cell line model to study chromatin dynamics.
Conducted proteome-wide analyses to identify chromatin organization components associated with HIRA.
Used FRAP and FLIM-FRET microscopy to observe chromatin changes following HIRA downregulation.
HIRA knockdown caused increased chromatin compaction and altered spatial distribution towards the nuclear periphery.
Elevations in H3K9me3 and HP1 levels linked to the activation of the SETDB1 pathway correlated with chromatin condensation.
HIRA loss led to reduced expression of the BCR-ABL fusion protein, impacting cell proliferation.

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Implication

Shows HIRA-SETDB1-H3K9me3 axis regulates chromatin in leukemia cells, suggesting new therapy avenues.

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Cite This Study

Shirude et al. (2026) studied this question.

synapsesocial.com/papers/69f2f1471e5f7920c6386f41 https://doi.org/10.1016/j.jbc.2026.113081

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HIRA-SETDB1-H3K9me3 axis regulates chromatin architecture in leukemia cells

Key Points

No abstract yet

Implication

Discussion

Cite This Study

HIRA-SETDB1-H3K9me3 axis regulates chromatin architecture in leukemia cells

Key Points

No abstract yet

Implication

Discussion

Cite This Study

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