PMID- 20693526
OWN - NLM
STAT- MEDLINE
DCOM- 20110131
LR  - 20240322
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 38
IP  - 22
DP  - 2010 Dec
TI  - ChIPing the cistrome of PXR in mouse liver.
PG  - 7943-63
LID - 10.1093/nar/gkq654 [doi]
AB  - 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.
FAU - Cui, Julia Yue
AU  - Cui JY
AD  - Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas 
      Medical Center, Kansas City, KS 66160, USA.
FAU - Gunewardena, Sumedha S
AU  - Gunewardena SS
FAU - Rockwell, Cheryl E
AU  - Rockwell CE
FAU - Klaassen, Curtis D
AU  - Klaassen CD
LA  - eng
GR  - RR021940/RR/NCRR NIH HHS/United States
GR  - R01 ES009716/ES/NIEHS NIH HHS/United States
GR  - R01 ES013714/ES/NIEHS NIH HHS/United States
GR  - RR016475/RR/NCRR NIH HHS/United States
GR  - ES013714/ES/NIEHS NIH HHS/United States
GR  - R01 DK081461/DK/NIDDK NIH HHS/United States
GR  - R01 ES009649/ES/NIEHS NIH HHS/United States
GR  - P20 RR021940/RR/NCRR NIH HHS/United States
GR  - HD002528/HD/NICHD NIH HHS/United States
GR  - DK081461/DK/NIDDK NIH HHS/United States
GR  - ES009716/ES/NIEHS NIH HHS/United States
GR  - ES009649/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100806
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Pregnane X Receptor)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Steroid)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Chromatin Immunoprecipitation
MH  - DNA/chemistry/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epigenesis, Genetic
MH  - Gene Expression Profiling
MH  - Genome
MH  - Inactivation, Metabolic/genetics
MH  - Liver/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oligonucleotide Array Sequence Analysis
MH  - Polymerase Chain Reaction
MH  - Pregnane X Receptor
MH  - RNA, Messenger/biosynthesis
MH  - Receptors, Steroid/*metabolism
MH  - Repetitive Sequences, Nucleic Acid
MH  - *Response Elements
MH  - Sequence Analysis, DNA
PMC - PMC3001051
EDAT- 2010/08/10 06:00
MHDA- 2011/02/01 06:00
PMCR- 2010/08/06
CRDT- 2010/08/10 06:00
PHST- 2010/08/10 06:00 [entrez]
PHST- 2010/08/10 06:00 [pubmed]
PHST- 2011/02/01 06:00 [medline]
PHST- 2010/08/06 00:00 [pmc-release]
AID - gkq654 [pii]
AID - 10.1093/nar/gkq654 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2010 Dec;38(22):7943-63. doi: 10.1093/nar/gkq654. Epub 2010 
      Aug 6.