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Related Concept Videos

Histone Modification02:32

Histone Modification

17.6K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
17.6K

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A Data-Driven Approach to Quantifying Immune States in Sepsis
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Sepsis induces specific changes in histone modification patterns in human monocytes.

Sebastian Weiterer1, Florian Uhle2, Christoph Lichtenstern2

  • 1Department of Anaesthesiology, Heidelberg University Hospital, Heidelberg, Germany; German Centre for Infection Research (DZIF), partner site Giessen-Marburg-Langen, Giessen, Germany.

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Sepsis alters immune cell gene regulation by changing histone modifications at specific gene promoters. These precise epigenetic changes in monocytes offer insights into sepsis-induced immune dysfunction.

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Area of Science:

  • Immunology
  • Epigenetics
  • Genomics

Background:

  • Sepsis is a leading cause of death in intensive care units globally.
  • The systemic inflammatory response in sepsis involves complex cellular changes.
  • Epigenetic mechanisms, such as histone modifications, are crucial for immune regulation but their role in sepsis remains unclear.

Purpose of the Study:

  • To investigate genome-wide histone modifications in monocytes during human sepsis.
  • To identify specific epigenetic changes associated with sepsis-induced immune responses.

Main Methods:

  • Combined chromatin immunoprecipitation and high-throughput sequencing (ChIP-seq).
  • Analysis of histone 3 lysine 4 trimethylation, lysine 27 trimethylation, and lysine 9 acetylation.
  • Monocytes isolated from healthy donors and sepsis patients.

Main Results:

  • High correlation of chromatin marks across patients and with healthy controls.
  • Identification of distinct promoter regions with significant enrichment or depletion of histone marks in sepsis.
  • Enrichment of immune function genes, including HLA family and CIITA, among differentially regulated genes.

Conclusions:

  • Sepsis induces selective and precise changes in chromatin modifications at immunologically relevant gene promoters.
  • These findings elucidate fundamental regulatory mechanisms underlying monocyte functional changes in sepsis.
  • This study provides novel insights into the epigenetic landscape of sepsis.