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bioRxiv · 10.64898/2026.10.13.758977

Coffee induces chromatin structural changes associated with histone H4K16 hypoacetylation

Tanaka, Y.·Cho, Y.·Suwabe, Y.·Misaki, S.·Uchidaya, R.·Aoyama, K.
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Abstract

Histone acetylation plays a critical role in the regulation of chromatin structure and gene expression. Among histone acetylation marks, acetylation of histone H4 at lysine 16 (H4K16ac) is particularly important for the maintenance of chromatin organization. We previously identified a reduction in H4K16ac following coffee treatment through mass spectrometry-based histone modification profiling. In the present study, we investigated the effects of coffee on H4K16ac levels, chromatin structure, and gene expression. Western blotting and immunofluorescence analyses confirmed that coffee treatment reduced H4K16ac levels in a cell type-dependent manner. Notably, H4K16ac was reduced in HCT116 cells, in which H3K27ac was not decreased by coffee treatment. Quantitative analysis of DAPI-stained nuclei revealed a significant increase in the coefficient of variation of nuclear fluorescence intensity following coffee treatment, indicating alterations in chromatin structure. Furthermore, integrative analysis of publicly available H4K16ac chromatin immunoprecipitation sequencing (ChIP-seq) data and previously generated RNA sequencing (RNA-seq) data revealed that H4K16ac-enriched genes exhibited transcriptional changes following coffee treatment in K562 cells, including the downregulation of MYC-associated genes. Together, these findings demonstrate that coffee treatment induces alterations in chromatin structure accompanied by H4K16 hypoacetylation and suggest a potential association between these epigenetic changes and transcriptional regulation.

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Tanaka, Y., Cho, Y., Suwabe, Y., Misaki, S., Uchidaya, R., Aoyama, K.. 2026-10-20. Coffee induces chromatin structural changes associated with histone H4K16 hypoacetylation. https://doi.org/10.64898/2026.10.13.758977

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