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bioRxiv · 10.64898/2026.03.08.708675

ATAD2 BRD mediates liquid-liquid phase separation of ATAD2 to promote histone acetylation

Shu, C.·Gong, Z.·Wang, Y.·Zhang, Y.·Liu, M.·Zhang, X.·Zeng, D.
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Abstract

ATAD2 possesses a C-terminal bromodomain (BRD) that plays a critical role in recognizing and binding to acetylated lysine residues. However, because the native intracellular structure of ATAD2 remains poorly defined, the mechanisms by which the ATAD2 BRD recruits acetylated histones and the regulatory pathways involved are not yet understood. In this study, we report that the ATAD2 BRD mediates the formation of liquid-liquid phase separation (LLPS) of ATAD2 in cells. This phase separation promotes the process of histone H4 acetylation, leading to the up-regulation of C-MYC, CCND3, and ATF2 gene expression and the facilitation of chromatin remodeling. Our findings elucidate a vital function of ATAD2, wherein BRD-mediated LLPS drives histone acetylation to promote cellular chromatin remodeling.

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Shu, C., Gong, Z., Wang, Y., Zhang, Y., Liu, M., Zhang, X., Zeng, D.. 2026-03-10. ATAD2 BRD mediates liquid-liquid phase separation of ATAD2 to promote histone acetylation. https://doi.org/10.64898/2026.03.08.708675

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