Microbiota-derived metabolite promotes HDAC3 activity in the gut

Posted by: | August 17, 2023 | Comments


The coevolution of mammalian hosts and their beneficial commensal microbes has led to development of a symbiotic host-microbiota relationship. Epigenetic machinery permits mammalian cells to integrate environmental signals, however, how these pathways are finely tuned by diverse cues from commensal bacteria is not well understood. Here, we reveal a highly selective pathway through which microbiota-derived inositol phosphate regulates histone deacetylase 3 (HDAC3) activity in the intestine. Despite abundant HDAC inhibitors in the intestine such as butyrate, we unexpectedly found that HDAC3 activity was sharply increased in intestinal epithelial cells (IECs) of microbiota-replete mice compared to germ-free mice. This discordance was reconciled by finding that commensal bacteria, including E. coli, stimulated HDAC activity through metabolism of phytate and inositol trisphosphate production.

Read more at: Nature

Shu-en Wu, Seika Hashimoto-Hill, Vivienne Woo, Emily M. Eshleman, Jordan Whitt, Laura Engleman, Rebekah Karns, Lee A. Denson, David B. Haslam & Theresa Alenghat. Nature. DOI: https://doi.org/10.1038/s41586-020-2604-2. 30 July 2023.

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