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.

Müller, Kolesnikova, Doudin, et al. reveal a structural mechanism for residue-specific nucleosome acetylation by capturing the MSL histone acetyltransferase during catalysis. Their findings provide a foundation for understanding how H4K16 acetylation links transcription to changes in chromatin structure, a mechanism essential for Drosophila dosage compensation and implicated in human disease.

Cell Death & Disease - C8orf33 dictates DNA double-strand break repair choice by modulating KAT8-mediated H4K16 acetylation

The RNA-binding protein hangover is essential for several stress responses in Drosophila melanogaster. Here, we discover a novel function of hangover in the regulation of gene expression. Hangover bin...

Read the full paper: Ailanthone alleviates septic cardiomyopathy by attenuating MYST histone acetyltransferase 1 (MOF)-mediated H4K16 lactylation-driven inflammation

Zheng et al. reveal a bromodomain-dependent role for BRD2 in transcriptional initiation and demonstrate that BRD2’s bromodomains anchor it to chromatin via MOF-acetylated histone H4K16. BRD2’s C-terminal domain facilitates interaction with RNA Pol II basal initiation factor TFIID. They also show that different BET domains have different acetyl-histone preferences.

Nitsch et al. show that short-chain acylations of histone H4K16, acetylation (C2), propionylation (C3), and butyrylation (C4) modulate chromatin structure in vitro. These effects can translate in vivo into balanced transcription responses under metabolic stress. This study provides insights into how different H4K16 acylations modulate chromatin structure and function.

Zheng et al. reveal a bromodomain-dependent role for BRD2 in transcriptional initiation and demonstrate that BRD2’s bromodomains anchor it to chromatin via MOF-acetylated histone H4K16. BRD2’s C-terminal domain facilitates interaction with RNA Pol II basal initiation factor TFIID. They also show that different BET domains have different acetyl-histone preferences.

Nitsch et al. show that short-chain acylations of histone H4K16, acetylation (C2), propionylation (C3), and butyrylation (C4) modulate chromatin structure in vitro. These effects can translate in vivo into balanced transcription responses under metabolic stress. This study provides insights into how different H4K16 acylations modulate chromatin structure and function.

Nitsch et al. show that short-chain acylations of histone H4K16, acetylation (C2), propionylation (C3), and butyrylation (C4) modulate chromatin structure in vitro. These effects can translate in vivo...

PubMed link