PMID- 8754834
OWN - NLM
STAT- MEDLINE
DCOM- 19960920
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 16
IP  - 8
DP  - 1996 Aug
TI  - Isolation of a novel retinoic acid-responsive gene by selection of genomic 
      fragments derived from CpG-island-enriched DNA.
PG  - 4337-48
AB  - One of the primary goals in transcription factor research is the elucidation of 
      the genetic networks controlled by a factor or by members of a family of closely 
      related factors. The pleiotropic effects of retinoic acid (PA) in the developing 
      and adult animal are mediated by ligand-inducible transcription factors (RA 
      receptors [RARs] and retinoid X receptors [RXRs]) that belong to the superfamily 
      of nuclear receptors. Regulatory regions of PA effector genes contain RAR and RXR 
      binding sites (RAR elements [RAREs] and RXR elements [RXREs]) that generally 
      consist of direct or everted repeats of the core half-site motif, (A/G)G(G/T)TCA. 
      In order to identify novel genes regulated by RA, we devised a selection strategy 
      based on the premise that regulatory regions of a large number of housekeeping 
      and tissue-specific genes are embodied within CpG island DNA. In this method, 
      referred to as CpG-selected and amplified binding, fragments derived from the CpG 
      island fraction of the murine genome are selected by a gel mobility shift assay 
      using in vitro-transcribed and -translated RXR-RAR. Multiple rounds of selection 
      coupled with amplification of the fragments by PCR enabled us to clone a 
      population of CG-rich fragments of which approximately one-fifth contained 
      consensus RAREs or RXREs. Twelve genomic fragments containing novel response 
      elements are described, and the transcription unit associated with one of them, 
      NN-84AG, was characterized in detail. The mouse NN-84AG transcript is upregulated 
      by RA in F9 embryonal carcinoma cells and is homologous to an expressed sequence 
      tag (EST41159) derived from a human infant brain cDNA library. Cloning of the 
      murine NN8-4AG genomic sequence places the RXRE in the proximity of the 
      transcription initiation sites of the gene. Although sequence analysis indicates 
      that the EST41159 gene product is novel, a region of amino acid identity with 
      sequences of a yeast polypeptide of, as yet, unknown function and the Drosophila 
      trithorax protein suggests the presence of an evolutionarily and functionally 
      conserved domain. Our study demonstrates that transcription factor binding sites 
      and corresponding regulated genes can be identified by selecting fragments 
      derived from the CpG island fraction of the genome.
FAU - Shago, M
AU  - Shago M
AD  - Molecular Oncology Group, Royal Victoria Hospital, Montreal, Quebec, Canada.
FAU - Giguere, V
AU  - Giguere V
LA  - eng
SI  - GENBANK/U50383
SI  - GENBANK/U50384
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (DNA, Complementary)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Biological Evolution
MH  - Cloning, Molecular
MH  - *CpG Islands
MH  - DNA, Complementary/genetics
MH  - Gene Expression Regulation, Developmental
MH  - Genes
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Oligodeoxyribonucleotides/chemistry
MH  - *Promoter Regions, Genetic
MH  - RNA, Messenger/genetics
MH  - Receptors, Retinoic Acid/*metabolism
MH  - Sequence Alignment
MH  - Sequence Homology, Nucleic Acid
MH  - Tretinoin/*metabolism
MH  - Tumor Cells, Cultured
MH  - Up-Regulation
PMC - PMC231432
EDAT- 1996/08/01 00:00
MHDA- 1996/08/01 00:01
PMCR- 1996/08/01
CRDT- 1996/08/01 00:00
PHST- 1996/08/01 00:00 [pubmed]
PHST- 1996/08/01 00:01 [medline]
PHST- 1996/08/01 00:00 [entrez]
PHST- 1996/08/01 00:00 [pmc-release]
AID - 10.1128/MCB.16.8.4337 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1996 Aug;16(8):4337-48. doi: 10.1128/MCB.16.8.4337.