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Publications of the Week

Microbiota-Derived Acetate Activates Intestinal Innate Immunity via the Tip60 Histone Acetyltransferase Complex

By June 28, 2021No Comments

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This week we profile a recent publication in Immunity from Drs. Bat-Erdene Jugder (pictured, left)
and Layla Kamareddine in Dr. Paula Watnick’s (right) lab at Boston Children’s Hospital.

Can you provide a brief overview of your lab’s current research focus?

Enteroendocrine cells are rare intestinal cells that respond to microbial metabolites.  Dr. Paula Watnick’s laboratory at Boston Children’s Hospital studies regulatory mechanisms that control the metabolism of commensal and pathogenic intestinal bacteria and the host response.

What is the significance of the findings in this publication?

In the journal Immunity, Jugder et al now report that enteroendocrine cells take up bacterial fermentation products and use them to remodel chromatin, thus coordinating intestinal innate immunity and lipid metabolism. The authors show that acetate produced by the microbiota enters the cell through an acetate transporter he named Tarag. From there it is converted to acetyl-CoA and used by the histone acetyltransferase Tip60 complex to acetylate histone 2Av, which activates transcription of ecdysone-induced genes including the peptidoglycan receptor PGRP-LC. The authors propose that the increase in PGRP-LC transcription potentiates innate immune signaling in the intestine. This leads to increased antimicrobial peptide expression and increased expression of tachykinin, an inhibitor of lipid synthesis in the gut. This provides a template for how microbiota might influence the innate immune response of the intestinal epithelium. 

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