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December 8, 2025Blood

Deciphering the role of EP300 in maintaining the enhancer landscape and lineage-specific epigenetic vulnerability in multiple myeloma

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Authors

STSrikanth TalluriAJAdvait Joshi

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Overview

Investigation shows EP300 regulates enhancer activity in multiple myeloma, indicating its potential as a therapeutic target.

Key Points

  • This research aims to explore the role of EP300 in enhancer activity and epigenetic regulation in multiple myeloma.
  • Used shRNA and PROTAC JQAD1 to degrade EP300 in multiple myeloma cell lines.
  • Conducted cell viability, apoptosis, migration, and invasion assays.
  • Performed RNA sequencing for transcriptomic changes post EP300 loss.
  • Conducted ATAC-seq and ChIP-seq for chromatin profiling and enhancer function analysis.
  • Utilized CUT&RUN on plasma cells from multiple myeloma patients to examine EP300 dependency.
  • Decreased cell viability and increased apoptosis were observed following EP300 degradation.
  • Reduction in cell migration and invasion potential across multiple myeloma cell lines.
  • Profiling revealed global enhancer disruption and loss of H3K27ac in key regulatory regions.
  • Unique interactions of EP300 with specific proteins were identified through mass spectrometry.
  • Persistent EP300 dependency was confirmed in multiple myeloma, linked to high IRF4 expression.

Cite This Study

Talluri et al. (2025) studied this question.

synapsesocial.com/papers/69362f484fa91c937236d6ddhttps://doi.org/10.1182/blood-2025-5735
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Targeted degradation of CBP/p300 by CBPD-409 exhibits robust anti-myeloma activity2026
  2. 2P300/CBP acetyltransferase inhibition and degradation disrupt oncogenic transcriptional programs and reveal epigenetic vulnerabilities in multiple myeloma2025
  3. 3The epigenetic regulators EP300/CREBBP represent promising therapeutic targets in MLL-rearranged acute myeloid leukemia2024 · 19 citations
  4. 4Abstract LB028: Discovery and characterization of selective heterobifunctional degraders of EP300 in hematopoietic malignancies2024 · 1 citations
  5. 5Abstract 1828: Preclinical evaluation of selective and potent EP300 degraders demonstrates robust antitumor activity and favorable tolerability in hematologic malignancies.2026