Promoter anchored interaction landscape of THP-1 macrophages captures early immune response processes

Cell Immunol. 2020 Sep:355:104148. doi: 10.1016/j.cellimm.2020.104148. Epub 2020 Jun 12.

Abstract

Macrophages are highly plastic immune cells with temporally distinct transcriptome changes upon lipopolysaccride (LPS) activation. However, to what extent transcriptome reprogramming is mediated via spatial chromatin looping is not well studied. We generated high resolution chromatin interaction maps for LPS-stimulated THP-1 macrophages (0 and 2 h) using capture Hi-C. Success of LPS stimulation was validated with transcriptome sequencing. Circa 2900 genes changed their interaction profile upon LPS stimulation and those gaining interactions were enriched for LPS response relevant processes, suggesting a substantial role for distal regulation. Immune and cardiovascular risk variants were enriched within the interacting regions, thereby providing insights into macrophage biology.

Keywords: Capture Hi-C; Chi-C; Genome wide association study (GWAS); HiCap; Lipopolysaccharide (LPS); Macrophages; THP-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin / genetics
  • Chromosome Mapping / methods
  • Gene Expression Profiling / methods
  • Genome-Wide Association Study / methods
  • Humans
  • Immunity / genetics*
  • Immunity / immunology
  • Lipopolysaccharides / pharmacology
  • Macrophages / cytology
  • Macrophages / immunology*
  • Macrophages / metabolism*
  • Promoter Regions, Genetic / genetics
  • THP-1 Cells / metabolism
  • Transcriptome / genetics

Substances

  • Chromatin
  • Lipopolysaccharides