Recent advances in the development of peptide-based inhibitors targeting epigenetic readers of histone lysine acetylation and methylation marks

Liu, Sha; Li, Xin; Li, Xiang

doi:10.1016/j.cbpa.2023.102334

Cited by 5 publications

(1 citation statement)

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“…For example, histones, which are scaffolding proteins for chromatin compaction in eukaryotic nuclei, are subjects to diverse PTMs . These histone marks can serve as docking hubs for the binding of protein effectors (or readers) to chromatin, enabling transmission of messages carried by the marks to downstream chromatin-templated events. − YEATS domains are a family of newly identified readers of histone lysine acetylation (Kac) and crotonylation (Kcr). − The human genome encodes four YEATS domain-containing proteins (YCPs), namely, AF9, ENL, GAS41, and YEATS2. , Recent studies have revealed associations between aberrant YEATS-dependent readouts of histone Kac/Kcr marks and human diseases, especially cancer. − Tools and/or methods that facilitate the interrogation of YEATS–Kac/Kcr interactions in different biological contexts would be helpful to comprehensively understand the roles played by YEATS domains in chromatin biology. − …”

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confidence: 99%

Genetically Encoded Epitope Tag for Probing Lysine Acylation-Mediated Protein–Protein Interactions

Tian,

Li,

2024

ACS Chem. Biol.

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Histone lysine acetylation (Kac) and crotonylation (Kcr) marks mediate the recruitment of YEATS domains to chromatin. In this way, YEATS domain-containing proteins such as AF9 participate in the regulation of DNA-templated processes. Our previous study showed that the replacement of Kac/Kcr by a 2-furancarbonyllysine (Kfu) residue led to greatly enhanced affinity toward the AF9 YEATS domain, rendering Kfu-containing peptides useful chemical tools to probe the AF9 YEATS–Kac/Kcr interactions. Here, we report the genetic incorporation of Kfu in Escherichia coli and mammalian cells through the amber codon suppression technology. We develop a Kfu-containing epitope tag, termed RAY-tag, which can robustly and selectively engage with the AF9 YEATS domain in vitro and in cellulo. We further demonstrate that the fusion of RAY-tag to different protein modules, including fluorescent proteins and DNA binding proteins, can facilitate the interrogation of the histone lysine acylation-mediated recruitment of the AF9 YEATS domain in different biological contexts.

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