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Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases.

ABSTRACT: The recently discovered histone post-translational modification crotonylation connects cellular metabolism to gene regulation. Its regulation and tissue-specific functions are poorly understood. We characterize histone crotonylation in intestinal epithelia and find that histone H3 crotonylation at lysine 18 is a surprisingly abundant modification in the small intestine crypt and colon, and is linked to gene regulation. We show that this modification is highly dynamic and regulated during the cell cycle. We identify class I histone deacetylases, HDAC1, HDAC2, and HDAC3, as major executors of histone decrotonylation. We show that known HDAC inhibitors, including the gut microbiota-derived butyrate, affect histone decrotonylation. Consistent with this, we find that depletion of the gut microbiota leads to a global change in histone crotonylation in the colon. Our results suggest that histone crotonylation connects chromatin to the gut microbiota, at least in part, via short-chain fatty acids and HDACs.

SUBMITTER: Fellows R

PROVIDER: S-EPMC5760624 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases.

Fellows Rachel R Denizot Jérémy J Stellato Claudia C Cuomo Alessandro A Jain Payal P Stoyanova Elena E Balázsi Szabina S Hajnády Zoltán Z Liebert Anke A Kazakevych Juri J Blackburn Hector H Corrêa Renan Oliveira RO Fachi José Luís JL Sato Fabio Takeo FT Ribeiro Willian R WR Ferreira Caroline Marcantonio CM Perée Hélène H Spagnuolo Mariangela M Mattiuz Raphaël R Matolcsi Csaba C Guedes Joana J Clark Jonathan J Veldhoen Marc M Bonaldi Tiziana T Vinolo Marco Aurélio Ramirez MAR Varga-Weisz Patrick P

Nature communications 20180109 1

The recently discovered histone post-translational modification crotonylation connects cellular metabolism to gene regulation. Its regulation and tissue-specific functions are poorly understood. We characterize histone crotonylation in intestinal epithelia and find that histone H3 crotonylation at lysine 18 is a surprisingly abundant modification in the small intestine crypt and colon, and is linked to gene regulation. We show that this modification is highly dynamic and regulated during the cel ...[more]

PMID: 29317660

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Project description:BackgroundFermented Aloe leaf juice is a commonly used food supplement in Japan. In a previous study, fermentation of A. arborescence juice was performed and the presence of short-chain fatty acids (SCFAs) was confirmed and quantified. Samples were collected before and after the fermentation process to be subjected, in the present study, to DNA extraction, 16S rRNA gene (V3-V4 regions) amplification, and sequencing by the next-generation Illumina MiSeq sequencer. Our work aims to analyze the sequences to assess the bacterial diversity in the juice before and after fermentation, identify the beneficial microbes responsible for the production of SCFAs, and evaluate some of the biological activities of the fermented juice.ResultsData revealed the richness and diversity of the bacterial community in the fermented juice compared to the unfermented control. Relative abundance of bacterial phyla showed that the majority of the microbial community in the test samples corresponded to Pseudomonadota (unfermented; 10.4%, fermented; 76.36%), followed by Bacillota (unfermented; 4.71%, fermented; 17.13%) and then Bacteroidota (unfermented; 0.57%, fermented; 1.64%). For the fermented sample, 84% of Bacillota were lactobacilli. A hierarchically clustered heatmap revealed that Lactobacillus was the most abundant genus in both samples suggesting its involvement in the production of SCFAs. To assess potential health benefits, the anticancer efficacy of the fermented product of A. arborescens was investigated against colorectal cancer (IC50 = 3.5 µg/ml) and liver cancer (IC50 = 6.367 µg/ml) compared to the normal peripheral blood mononuclear cells (PBMCs). Flow cytometric analysis of the cell cycle pattern revealed remarkable population arrest in G0 and G1, however, the highest percentages were mainly in the G1 phase for Hep-G2 (40.1%) and HCT-116 (53.2%) cell lines. This effect was accompanied by early apoptotic profiles of HCT-116 (36.9%) and late apoptosis for Hep-G2 (17.3%). Furthermore, immunomodulatory properties demonstrated a significantly (p < 0.001) reduced percentage of induced TNF-α while enhancing IFN-γ dramatically. For antimicrobial activities, marked broad-spectrum activities were recorded against some bacterial and fungal pathogens (17-37 mm inhibition zone diameter range).ConclusionTherefore, this study affords the basis of bacterial community composition in fermented A. arborescens juice as well as its potential biological benefits.

Dataset Information

Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases.

Publications

Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases.

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