Year: 2025
Type: article
Abstract: The YEATS domain is an evolutionarily conserved epigenetic reader that specifically recognizes post-translational lysine acylation on histone tails and plays a crucial role in chromatin remodeling and transcriptional regulation. Four human YEATS domain-containing proteins, ENL, AF9, YEATS2, and GAS41, have been implicated in the pathogenesis of various malignancies. This review provides an overview of the structural basis for the YEATS domain's recognition of diverse acyllysine post-translational modifications and discusses the disease-related consequences of aberrant YEATS activity. Emphasis is placed on recent progress in the development of chemical modulators, including peptide-based inhibitors, small molecules, and proteolysis-targeting chimeras (PROTACs), that represent promising strategies for the selective targeting of YEATS domains. These developments underscore the potential of YEATS-directed therapies in epigenetic drug discovery.
Source: ACS Chemical Biology
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Funders: Welch Foundation, Texas AgriLife Research, Cancer Prevention and Research Institute of Texas, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, University of Colorado School of Medicine, Anschutz Medical Campus
Awards: G1195052402, G1670116962, G175929860, G1995594130, A Multiplatform Approach to Develop ENL-Targeting Molecules as Drug Candidates for Acute Myeloid Leukemia, The Development of Reversible Chemogenetic Switches for Chimeric Antigen Receptor T Cell Therapy, G6056526929, G6553094674, The acquisition of an instrument suite to set up a high-throughput screening core at Texas A&M University, G9000081631, G9000091077, G9000231017, G9000257845
OpenAlex ID: W4412201209