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

[en] 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.

Disciplines :

Genetics & genetic processes

Author, co-author :

Fellows, Rachel

Denizot, Jérémy

Stellato, Claudia

Cuomo, Alessandro

Jain, Payal

Stoyanova, Elena

Balázsi, Szabina

Hajnády, Zoltán

Liebert, Anke

Kazakevych, Juri

More authors (16 more)

Language :

English

Title :

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

Publication date :

2018

Journal title :

Nature Communications

eISSN :

2041-1723

Publisher :

Nature Publishing Group, United Kingdom

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 22 May 2019

Statistics

Number of views

42 (4 by ULiège)

Number of downloads

0 (0 by ULiège)

More statistics

Scopus citations^®

301

Scopus citations^®
without self-citations

289

OpenCitations

255

Bibliography

Keating, S. T. &El-Osta, A. Epigenetics and metabolism. Circ. Res. 116, 715-736 (2015).
Tan, M. et al. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell 146, 1016-1028 (2011).
Chen, Y. et al. Lysine propionylation and butyrylation are novel posttranslational modifications in histones. Mol. Cell. Proteom. 6, 812-819 (2007).
Goudarzi, A. et al. Dynamic competing histone H4 K5K8 acetylation and butyrylation are hallmarks of highly active gene promoters. Mol. Cell 62, 169-180 (2016).
Xie, Z. et al. Metabolic regulation of gene expression by histone lysine β-hydroxybutyrylation. Mol. Cell 62, 194-206 (2016).
Sabari, B. R. et al. Intracellular crotonyl-CoA stimulates transcription through p300-catalyzed histone crotonylation. Mol. Cell 58, 203-215 (2015).
Sabari, B. R., Zhang, D., Allis, C. D. &Zhao, Y. Metabolic regulation of gene expression through histone acylations. Nat. Rev. Mol. Cell. Biol. 18, 90-101 (2016).
Lin, H., Su, X. &He, B. Protein lysine acylation and cysteine succination by intermediates of energy metabolism. ACS Chem. Biol. 7, 947-960 (2012).
Zhao, D. et al. YEATS2 is a selective histone crotonylation reader. Cell Res. 26, 629-632 (2016).
Li, Y. et al. Molecular coupling of histone crotonylation and active transcription by AF9 YEATS domain. Mol. Cell 62, 181-193 (2016).
Xiong, X. et al. Selective recognition of histone crotonylation by double PHD fingers of MOZ and DPF2. Nat. Chem. Biol. 12, 1111-1118 (2016).
Andrews, F. H. et al. The Taf14 YEATS domain is a reader of histone crotonylation. Nat. Chem. Biol. 12, 396-398 (2016).
Kasubuchi, M., Hasegawa, S., Hiramatsu, T., Ichimura, A. &Kimura, I. Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients 7, 2839-2849 (2015).
Koh, A., De Vadder, F., Kovatcheva-Datchary, P. &Bäckhed, F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 165, 1332-1345 (2016).
Donohoe, D. R. et al. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 13, 517-526 (2011).
Krautkramer, K. A. et al. Diet-microbiota interactions mediate global epigenetic programming in multiple host tissues. Mol. Cell 64, 982-992 (2016).
Candido, E. P., Reeves, R. &Davie, J. R. Sodium butyrate inhibits histone deacetylation in cultured cells. Cell 14, 105-113 (1978).
Balasubramanian, S., Verner, E. &Buggy, J. J. Isoform-specific histone deacetylase inhibitors: the next step? Cancer Lett. 280, 211-221 (2009).
Taddei, A., Maison, C., Roche, D. &Almouzni, G. Reversible disruption of pericentric heterochromatin and centromere function by inhibiting deacetylases. Nat. Cell Biol. 3, 114-120 (2001).
Wegener, D., Wirsching, F., Riester, D. &Schwienhorst, A. A fluorogenic histone deacetylase assay well suited for high-throughput activity screening. Chem. Biol. 10, 61-68 (2003).
Halley, F. et al. A bioluminogenic HDAC activity assay. J. Biomol. Screen. 16, 1227-1235 (2011).
Henkes, L. M., Haus, P., Jäger, F., Ludwig, J. &Meyer-Almes, F.-J. Synthesis and biochemical analysis of 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoro-N-hydroxyoctanediamides as inhibitors of human histone deacetylases. Bioorg. Med. Chem. 20, 985-995 (2012).
Hoffmann, K., Brosch, G., Loidl, P. &Jung, M. A non-isotopic assay for histone deacetylase activity. Nucleic Acids Res. 27, 2057-2058 (1999).
Schultz, B. E. et al. Kinetics and comparative reactivity of human class I and class IIb histone deacetylases. Biochemistry 43, 11083-11091 (2004).
Stilling, R. M. et al. The neuropharmacology of butyrate: the bread and butter of the microbiota-gut-brain axis? Neurochem. Int. 99, 110-132 (2016).
Sobel, R. E., Cook, R. G., Perry, C. A., Annunziato, A. T. &Allis, C. D. Conservation of deposition-related acetylation sites in newly synthesized histones H3 and H4. Proc. Natl Acad. Sci. USA 92, 1237-1241 (1995).
Jasencakova, Z. et al. Replication stress interferes with histone recycling and predeposition marking of new histones. Mol. Cell 37, 736-743 (2010).
Annunziato, A. T. Assembling chromatin: the long and winding road. Biochim. Biophys. Acta. 1819, 196-210 (2012).
Taddei, A., Roche, D., Sibarita, J. B., Turner, B. M. &Almouzni, G. Duplication and maintenance of heterochromatin domains. J. Cell Biol. 147, 1153-1166 (1999).
Bhaskara, S. et al. Hdac3 Is essential for the maintenance of chromatin structure and genome stability. Cancer Cell 18, 436-447 (2010).
Bhaskara, S. et al. Histone deacetylases 1 and 2 maintain S-phase chromatin and DNA replication fork progression. Epigenetics Chromatin 6, 27 (2013).
Krämer, O. H. et al. The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2. EMBO J. 22, 3411-3420 (2003).
Zhu, P. et al. Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis. Cancer Cell 5, 455-463 (2004).
Ashktorab, H. et al. Global histone H4 acetylation and HDAC2 expression in colon adenoma and carcinoma. Dig. Dis. Sci. 54, 2109-2117 (2009).
Wei, W. et al. Class I histone deacetylases are major histone decrotonylases: evidence for critical and broad function of histone crotonylation in transcription. Cell Res. 27, 898-915 (2017).
Madsen, A. S. &Olsen, C. A. Profiling of substrates for zinc-dependent lysine deacylase enzymes: HDAC3 exhibits decrotonylase activity in vitro. Angew. Chem. Int. Ed. Engl. 51, 9083-9087 (2012).
Xu, W. et al. Global profiling of crotonylation on non-histone proteins. Cell Res. 27, 946-949 (2017).
Ceccacci, E. &Minucci, S. Inhibition of histone deacetylases in cancer therapy: lessons from leukaemia. Br. J. Cancer 114, 605-611 (2016).
Li, Y. &Seto, E. HDACs and HDAC inhibitors in cancer development and therapy. Cold Spring Harb. Perspect. Med. 6, https://doi.org/10.1101/ cshperspect.a026831 (2016).
Barman, M. et al. Enteric salmonellosis disrupts the microbial ecology of the murine gastrointestinal tract. Infect. Immun. 76, 907-915 (2008).
Mendes, E. et al. Prophylactic supplementation of Bifidobacterium longum 51A protects mice from ovariectomy-induced exacerbated allergic airway inflammation and airway hyperresponsiveness. Front. Microbiol. 8, 1732 (2017).
Soldi, M., Cuomo, A. &Bonaldi, T. Improved bottom-up strategy to efficiently separate hypermodified histone peptides through ultra-HPLC separation on a bench top Orbitrap instrument. Proteomics 14, 2212-2225 (2014).
Cuomo, A., Soldi, M. &Bonaldi, T. SILAC-based quantitative strategies for accurate histone posttranslational modification profiling across multiple biological samples. Methods Mol. Biol. 1528, 97-119 (2017).
Rappsilber, J., Ishihama, Y. &Mann, M. Stop and go extraction tips for matrixassisted laser desorption/ionization, nanoelectrospray, and LC/MS sample pretreatment in proteomics. Anal. Chem. 75, 663-670 (2003).
Cuomo, A., Moretti, S., Minucci, S. &Bonaldi, T. SILAC-based proteomic analysis to dissect the "histone modification signature" of human breast cancer cells. Amino Acids 41, 387-399 (2011).
Tyanova, S., Temu, T. &Cox, J. The MaxQuant computational platform for mass spectrometry-based shotgun proteomics. Nat. Protoc. 11, 2301-2319 (2016).
Tyanova, S. et al. Visualization of LC-MS/MS proteomics data in MaxQuant. Proteomics 15, 1453-1456 (2015).
Jung, H. R., Pasini, D., Helin, K. &Jensen, O. N. Quantitative mass spectrometry of histones H3.2 and H3.3 in Suz12-deficient mouse embryonic stem cells reveals distinct, dynamic post-translational modifications at Lys-27 and Lys-36. Mol. Cell. Proteom. 9, 838-850 (2010).
Tyanova, S. et al. The Perseus computational platform for comprehensive analysis of (prote)omics data. Nat. Methods 13, 731-740 (2016).
Tou, L., Liu, Q. &Shivdasani, R. A. Regulation of mammalian epithelial differentiation and intestine development by class I histone deacetylases. Mol. Cell. Biol. 24, 3132-3139 (2004).
Sato, T. &Clevers, H. Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Science 340, 1190-1194 (2013).