ChIPing the cistrome of PXR in mouse liver

Nucleic Acids Res. 2010 Dec;38(22):7943-63. doi: 10.1093/nar/gkq654. Epub 2010 Aug 6.


The pregnane X receptor (PXR) is a key regulator of xenobiotic metabolism and disposition in liver. However, little is known about the PXR DNA-binding signatures in vivo, or how PXR regulates novel direct targets on a genome-wide scale. Therefore, we generated a roadmap of hepatic PXR bindings in the entire mouse genome [chromatin immunoprecipitation (ChIP)-Seq]. The most frequent PXR DNA-binding motif is the AGTTCA-like direct repeat with a 4 bp spacer [direct repeat (DR)-4)]. Surprisingly, there are also high motif occurrences with spacers of a periodicity of 5 bp, forming a novel DR-(5 n+4) pattern for PXR binding. PXR-binding overlaps with the epigenetic mark for gene activation (histone-H3K4-di-methylation), but not with epigenetic marks for gene suppression (DNA methylation or histone-H3K27-tri-methylation) (ChIP-on-chip). After administering a PXR agonist, changes in mRNA of most PXR-direct target genes correlate with increased PXR binding. Specifically, increased PXR binding triggers the trans-activation of critical drug-metabolizing enzymes and transporters. The mRNA induction of these genes is absent in PXR-null mice. The current work provides the first in vivo evidence of PXR DNA-binding signatures in the mouse genome, paving the path for predicting and further understanding the multifaceted roles of PXR in liver.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binding Sites
  • Chromatin Immunoprecipitation
  • DNA / chemistry
  • DNA / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Epigenesis, Genetic
  • Gene Expression Profiling
  • Genome
  • Inactivation, Metabolic / genetics
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Pregnane X Receptor
  • RNA, Messenger / biosynthesis
  • Receptors, Steroid / metabolism*
  • Repetitive Sequences, Nucleic Acid
  • Response Elements*
  • Sequence Analysis, DNA


  • Pregnane X Receptor
  • RNA, Messenger
  • Receptors, Steroid
  • DNA