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Histone butyrylation in the mouse intestine is mediated by the microbiota and associated with regulation of gene expression.
Gates, Leah A; Reis, Bernardo Sgarbi; Lund, Peder J; Paul, Matthew R; Leboeuf, Marylene; Djomo, Annaelle M; Nadeem, Zara; Lopes, Mariana; Vitorino, Francisca N; Unlu, Gokhan; Carroll, Thomas S; Birsoy, Kivanç; Garcia, Benjamin A; Mucida, Daniel; Allis, C David.
Afiliação
  • Gates LA; Laboratory of Chromatin Biology & Epigenetics, The Rockefeller University, New York, NY, USA. leah.gates@case.edu.
  • Reis BS; Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH, USA. leah.gates@case.edu.
  • Lund PJ; Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, USA.
  • Paul MR; Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • Leboeuf M; Department of Biochemistry and Molecular Biophysics, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
  • Djomo AM; Bioinformatics Resource Center, The Rockefeller University, New York, NY, USA.
  • Nadeem Z; Laboratory of Chromatin Biology & Epigenetics, The Rockefeller University, New York, NY, USA.
  • Lopes M; Laboratory of Chromatin Biology & Epigenetics, The Rockefeller University, New York, NY, USA.
  • Vitorino FN; Laboratory of Chromatin Biology & Epigenetics, The Rockefeller University, New York, NY, USA.
  • Unlu G; Hunter College of the City University of New York, Yalow Honors Scholar Program, New York, NY, USA.
  • Carroll TS; Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
  • Birsoy K; Department of Biochemistry and Molecular Biophysics, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
  • Garcia BA; Department of Biochemistry and Molecular Biophysics, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
  • Mucida D; Laboratory of Metabolic Regulation & Genetics, The Rockefeller University, New York, NY, USA.
  • Allis CD; Bioinformatics Resource Center, The Rockefeller University, New York, NY, USA.
Nat Metab ; 6(4): 697-707, 2024 Apr.
Article em En | MEDLINE | ID: mdl-38413806
ABSTRACT
Post-translational modifications (PTMs) on histones are a key source of regulation on chromatin through impacting cellular processes, including gene expression1. These PTMs often arise from metabolites and are thus impacted by metabolism and environmental cues2-7. One class of metabolically regulated PTMs are histone acylations, which include histone acetylation, butyrylation, crotonylation and propionylation3,8. As these PTMs can be derived from short-chain fatty acids, which are generated by the commensal microbiota in the intestinal lumen9-11, we aimed to define how microbes impact the host intestinal chromatin landscape, mainly in female mice. Here we show that in addition to acetylation, intestinal epithelial cells from the caecum and distal mouse intestine also harbour high levels of butyrylation and propionylation on lysines 9 and 27 of histone H3. We demonstrate that these acylations are regulated by the microbiota and that histone butyrylation is additionally regulated by the metabolite tributyrin. Tributyrin-regulated gene programmes are correlated with histone butyrylation, which is associated with active gene-regulatory elements and levels of gene expression. Together, our study uncovers a regulatory layer of how the microbiota and metabolites influence the intestinal epithelium through chromatin, demonstrating a physiological setting in which histone acylations are dynamically regulated and associated with gene regulation.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Histonas / Processamento de Proteína Pós-Traducional / Regulação da Expressão Gênica / Microbioma Gastrointestinal Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Histonas / Processamento de Proteína Pós-Traducional / Regulação da Expressão Gênica / Microbioma Gastrointestinal Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article