Inhibition of p300/CREBBP catalytic activity drives context-dependent transcriptional activation in AML
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The authors investigate how inhibition of the lysine acetyltransferase (KAT) activity of p300/CREBBP affects transcription in acute myeloid leukemia (AML). They find that this inhibition paradoxically enhances transcription by promoting cooperative transcription factor assembly and increasing H3K27 acetylation at specific regulatory elements, particularly those associated with interferon-stimulated genes. Their findings suggest a novel therapeutic strategy that combines KAT inhibition with interferon-alpha to drive AML cell death and improve treatment outcomes.
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