Ep300, also known as E1A-binding protein p300, is a histone acetyltransferase. It is crucial for epigenetic regulation as it acetylates histones, altering global chromatin structure and gene expression. This process is involved in various biological pathways such as cell-cycle regulation, differentiation, and fibrosis-related processes [1,4].

In hematologic malignancies, the bromodomain inhibitor CCS1477 can disrupt the recruitment of EP300/CBP to enhancer networks, inducing cell-cycle arrest and differentiation [1]. In high-risk neuroblastoma, EP300 controls enhancer acetylation by interacting with TFAP2β, and the PROTAC compound JQAD1, which targets EP300 for degradation, causes apoptosis in neuroblastoma cells [2]. In diffuse large B-cell lymphoma, CREBBP/EP300 mutations promote tumor progression by altering tumor-associated macrophage polarization via the FBXW7-NOTCH-CCL2/CSF1 axis [3].

In summary, EP300 plays essential roles in multiple biological processes and disease conditions. Studies using different models, such as inhibitors and PROTACs targeting EP300, have revealed its significance in malignancies, highlighting its potential as a therapeutic target in these disease areas.