Identification of Histone deacetylase (HDAC)‐Associated Proteins with DNA‐Programmed Affinity Labeling

Abstract

Histone deacetylase (HDAC) is a major class of deacetylation enzymes. Many HDACs exist in large protein complexes in cells and their functions strongly depend on the complex composition. The identification of HDAC‐associated proteins is highly important in understanding their molecular mechanisms. Although affinity probes have been developed to study HDACs, they were mostly targeting the direct binder HDAC, while other proteins in the complex remain underexplored. We report a DNA‐based affinity labeling method capable of presenting different probe configurations without the need for preparing multiple probes. Using one binding probe, 9 probe configurations were created to profile HDAC complexes. Notably, this method identified indirect HDAC binders that may be inaccessible to traditional affinity probes, and it also revealed new biological implications for HDAC‐associated proteins. This study provided a simple and broadly applicable method for characterizing protein‐protein interactions.

Efficacy and safety of histone deacetylase inhibitors in peripheral T-cell lymphoma: a systematic review and meta-analysis on prospective clinical trials

“…Histone deacetylases (HDACs) are indispensable to controlling protein deacetylation in cells. They play a vital role in the epigenetic modulation of biological processes and regulate protein degradation (6,7). However, the abnormal activity of HDACs is often related to disease progression (8), leading to increased attention to HDACs as therapeutic targets (9).…”