Inhibition of p300/CREBBP catalytic activity drives context-dependent transcriptional activation in AML - PubMed
5 hours ago
- #p300/CREBBP
- #AML
- #transcriptional activation
- Inhibition of p300/CREBBP catalytic activity in AML leads to paradoxical transcriptional activation.
- KAT inhibition retains p300/CREBBP, promotes cooperative TF assembly, and increases H3K27 acetylation at specific regulatory elements.
- IRF motif-enriched loci, including interferon-stimulated genes (ISGs), show pronounced effects with enhanced STAT1 recruitment.
- KAT inhibition converts ISG loci into transcriptionally active states, inducing cell-cycle arrest, differentiation, and apoptosis.
- Combining KAT inhibition with interferon-alpha synergistically enhances AML cell death and extends survival in models.
- Findings suggest translational potential for reprogramming interferon-driven programs via catalytic inhibition in AML.