PMID- 22661711
OWN - NLM
STAT- MEDLINE
DCOM- 20121011
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 287
IP  - 31
DP  - 2012 Jul 27
TI  - Retinoic acid receptors recognize the mouse genome through binding elements with 
      diverse spacing and topology.
PG  - 26328-41
LID - 10.1074/jbc.M112.361790 [doi]
AB  - Retinoic acid receptors (RARs) heterodimerize with retinoid X receptors (RXRs) 
      and bind to RA response elements (RAREs) in the regulatory regions of their 
      target genes. Although previous studies on limited sets of RA-regulated genes 
      have defined canonical RAREs as direct repeats of the consensus RGKTCA separated 
      by 1, 2, or 5 nucleotides (DR1, DR2, DR5), we show that in mouse embryoid bodies 
      or F9 embryonal carcinoma cells, RARs occupy a large repertoire of sites with 
      DR0, DR8, and IR0 (inverted repeat 0) elements. Recombinant RAR-RXR binds these 
      non-canonical spacings in vitro with comparable affinities to DR2 and DR5. Most 
      DR8 elements comprise three half-sites with DR2 and DR0 spacings. This specific 
      half-site organization constitutes a previously unrecognized but frequent 
      signature of RAR binding elements. In functional assays, DR8 and IR0 elements act 
      as independent RAREs, whereas DR0 does not. Our results reveal an unexpected 
      diversity in the spacing and topology of binding elements for the RAR-RXR 
      heterodimer. The differential ability of RAR-RXR bound to DR0 compared to DR2, 
      DR5, and DR8 to mediate RA-dependent transcriptional activation indicates that 
      half-site spacing allosterically regulates RAR function.
FAU - Moutier, Emmanuel
AU  - Moutier E
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/UDS, 
      1 Rue Laurent Fries, 67404 Illkirch Cedex, France.
FAU - Ye, Tao
AU  - Ye T
FAU - Choukrallah, Mohamed-Amin
AU  - Choukrallah MA
FAU - Urban, Sylvia
AU  - Urban S
FAU - Osz, Judit
AU  - Osz J
FAU - Chatagnon, Amandine
AU  - Chatagnon A
FAU - Delacroix, Laurence
AU  - Delacroix L
FAU - Langer, Diana
AU  - Langer D
FAU - Rochel, Natacha
AU  - Rochel N
FAU - Moras, Dino
AU  - Moras D
FAU - Benoit, Gerard
AU  - Benoit G
FAU - Davidson, Irwin
AU  - Davidson I
LA  - eng
SI  - GEO/GSE35599
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120601
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites
MH  - Binding, Competitive
MH  - Cells, Cultured
MH  - Chromatin Immunoprecipitation
MH  - Coculture Techniques
MH  - Consensus Sequence
MH  - Electrophoretic Mobility Shift Assay
MH  - Embryoid Bodies/metabolism
MH  - Genome
MH  - Mice
MH  - Protein Binding
MH  - Receptors, Retinoic Acid/chemistry/*metabolism
MH  - Repetitive Sequences, Nucleic Acid
MH  - *Response Elements
MH  - Retinoid X Receptors/chemistry/*metabolism
MH  - Sequence Analysis, DNA
MH  - Titrimetry
MH  - Transcription, Genetic
PMC - PMC3406717
EDAT- 2012/06/05 06:00
MHDA- 2012/10/12 06:00
PMCR- 2013/07/27
CRDT- 2012/06/05 06:00
PHST- 2012/06/05 06:00 [entrez]
PHST- 2012/06/05 06:00 [pubmed]
PHST- 2012/10/12 06:00 [medline]
PHST- 2013/07/27 00:00 [pmc-release]
AID - S0021-9258(20)73644-6 [pii]
AID - M112.361790 [pii]
AID - 10.1074/jbc.M112.361790 [doi]
PST - ppublish
SO  - J Biol Chem. 2012 Jul 27;287(31):26328-41. doi: 10.1074/jbc.M112.361790. Epub 
      2012 Jun 1.