Genome-wide landscape of liver X receptor chromatin binding and gene regulation in human macrophages

BMC Genomics. 2012 Jan 31;13:50. doi: 10.1186/1471-2164-13-50.

Abstract

Background: The liver X receptors (LXRs) are oxysterol sensing nuclear receptors with multiple effects on metabolism and immune cells. However, the complete genome-wide cistrome of LXR in cells of human origin has not yet been provided.

Results: We performed ChIP-seq in phorbol myristate acetate-differentiated THP-1 cells (macrophage-type) after stimulation with the potent synthetic LXR ligand T0901317 (T09). Microarray gene expression analysis was performed in the same cellular model. We identified 1357 genome-wide LXR locations (FDR < 1%), of which 526 were observed after T09 treatment. De novo analysis of LXR binding sequences identified a DR4-type element as the major motif. On mRNA level T09 up-regulated 1258 genes and repressed 455 genes. Our results show that LXR actions are focused on 112 genomic regions that contain up to 11 T09 target genes per region under the control of highly stringent LXR binding sites with individual constellations for each region. We could confirm that LXR controls lipid metabolism and transport and observed a strong association with apoptosis-related functions.

Conclusions: This first report on genome-wide binding of LXR in a human cell line provides new insights into the transcriptional network of LXR and its target genes with their link to physiological processes, such as apoptosis.The gene expression microarray and sequence data have been submitted collectively to the NCBI Gene Expression Omnibus http://www.ncbi.nlm.nih.gov/geo under accession number GSE28319.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Binding Sites
  • Cell Line
  • Chromatin / metabolism*
  • Down-Regulation
  • Gene Expression Regulation*
  • Genome-Wide Association Study*
  • Humans
  • Lipid Metabolism
  • Liver X Receptors
  • Macrophages / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Orphan Nuclear Receptors / antagonists & inhibitors
  • Orphan Nuclear Receptors / metabolism*
  • Protein Binding
  • Up-Regulation

Substances

  • Chromatin
  • Liver X Receptors
  • Orphan Nuclear Receptors

Associated data

  • GEO/GSE28319