PMID- 11113125
OWN - NLM
STAT- MEDLINE
DCOM- 20010719
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 10
DP  - 2001 Mar 9
TI  - Chromatin assembly enhances binding to the CYP2B1 phenobarbital-responsive unit 
      (PBRU) of nuclear factor-1, which binds simultaneously with constitutive 
      androstane receptor (CAR)/retinoid X receptor (RXR) and enhances CAR/RXR-mediated 
      activation of the PBRU.
PG  - 7559-67
AB  - Phenobarbital induction of CYP2B genes is mediated by a complex 
      phenobarbital-responsive enhancer (PBRU), which contains a binding site for 
      nuclear factor-1 (NF-1) flanked by two DR-4 nuclear receptor (NR) binding sites 
      for a heterodimer of constitutive androstane receptor (CAR) and retinoid X 
      receptor (RXR). To examine potential interactions between NF-1 and CAR/RXR, 
      binding of purified recombinant proteins to DNA, or to chromatin assembled using 
      Drosophila embryo extract, was examined. NF-1 and CAR/RXR bound simultaneously 
      and independently to the overlapping NF-1 and NR-1 sites; binding of CAR/RXR to 
      the NR-2 site was modestly increased by NF-1 binding; and CAR/RXR bound to a new 
      site in the PBRU region, designated NR-3. Assembly of plasmid DNA into chromatin 
      using Drosophila extract resulted in linearly phased nucleosomes in the PBRU 
      region. The apparent binding affinity of NF-1 was increased by about 10-fold in 
      assembled chromatin compared with DNA, whereas CAR/RXR binding was decreased. As 
      observed for DNA, however, simultaneous, largely independent, binding to the NF-1 
      and NR sites was observed. CAR-mediated transactivation of the PBRU in cultured 
      cells of hepatic origin was inhibited by mutations in the NF-1 site, and 
      overexpression of NF-1 increased CAR transactivation in HepG2 cells. These 
      studies demonstrate that NF-1 and CAR/RXR can both bind to the PBRU at the same 
      time and that chromatin assembly increases NF-1 binding, which is consistent with 
      previous in vivo footprinting studies in which the NF-1 site was occupied in 
      untreated animals and the NF-1 and flanking NR sites were occupied after 
      phenobarbital treatment. CAR-mediated trans-activation of the PBRU was increased 
      by NF-1, analogous to NF-1 effects on phenobarbital induction in previous 
      transient transfection studies and consistent with mediation of phenobarbital 
      induction by CAR.
FAU - Kim, J
AU  - Kim J
AD  - Departments of Molecular & Integrative Physiology and Cell & Structural Biology, 
      College of Medicine, University of Illinois at Urbana-Champaign, 61801, USA.
FAU - Min, G
AU  - Min G
FAU - Kemper, B
AU  - Kemper B
LA  - eng
GR  - GM39360/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20001211
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (Chromatin)
RN  - 0 (Constitutive Androstane Receptor)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (NFI Transcription Factors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 0 (Y-Box-Binding Protein 1)
RN  - 0 (YBX1 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2B1)
RN  - EC 3.1.21.1 (Deoxyribonuclease I)
RN  - YQE403BP4D (Phenobarbital)
SB  - IM
MH  - Amino Acid Motifs
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites
MH  - CCAAT-Enhancer-Binding Proteins/chemistry/*metabolism
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Chromatin/*chemistry/metabolism
MH  - Constitutive Androstane Receptor
MH  - Cytochrome P-450 CYP2B1/*chemistry/*metabolism
MH  - DNA Footprinting
MH  - *DNA-Binding Proteins
MH  - Deoxyribonuclease I/metabolism
MH  - Drosophila/embryology
MH  - Hepatocytes/metabolism
MH  - Humans
MH  - Liver/metabolism
MH  - Mice
MH  - Models, Genetic
MH  - Molecular Sequence Data
MH  - Mutation
MH  - NFI Transcription Factors
MH  - Nuclear Proteins
MH  - Phenobarbital/*pharmacology
MH  - Plasmids/metabolism
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Receptors, Cytoplasmic and Nuclear/chemistry/*metabolism
MH  - Receptors, Retinoic Acid/chemistry/*metabolism
MH  - Retinoid X Receptors
MH  - Sequence Homology, Nucleic Acid
MH  - Transcription Factors/chemistry/*metabolism
MH  - Transcriptional Activation
MH  - Y-Box-Binding Protein 1
EDAT- 2000/12/13 00:00
MHDA- 2001/07/20 10:01
CRDT- 2000/12/13 00:00
PHST- 2000/12/13 00:00 [pubmed]
PHST- 2001/07/20 10:01 [medline]
PHST- 2000/12/13 00:00 [entrez]
AID - S0021-9258(19)67213-3 [pii]
AID - 10.1074/jbc.M008090200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 Mar 9;276(10):7559-67. doi: 10.1074/jbc.M008090200. Epub 2000 
      Dec 11.