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Genetic and pharmacological inactivation of adenosine A2A receptor reveals an Egr-2-mediated transcriptional regulatory network in the mouse striatum.

Authors:Yu L, Haverty PM, Mariani J, Wang Y, Shen HY, Schwarzschild MA, Weng Z, Chen JF
Title:Genetic and pharmacological inactivation of adenosine A2A receptor reveals an Egr-2-mediated transcriptional regulatory network in the mouse striatum.
Journal:Physiological genomics Sep 2005 , Vol 23 , pp. 89-102
Abstract:The adenosine A2A receptor (A2AR) is highly expressed in the striatum, where it modulates motor and emotional behaviors. We used both microarray and bioinformatics analyses to compare gene expression profiles by genetic and pharmacological inactivation of A2AR and inferred an A2AR-controlled transcription network in the mouse striatum. A comparison between vehicle (VEH)-treated A2AR knockout (KO) mice (A2AR KO-VEH) and wild-type (WT) mice (WT-VEH) revealed 36 upregulated genes that were partially mimicked by treatment with SCH-58261 (SCH; an A2AR antagonist) and 54 downregulated genes that were not mimicked by SCH treatment. We validated the A2AR as a specific drug target for SCH by comparing A2AR KO-SCH and A2AR KO-VEH groups. The unique downregulation effect of A2AR KO was confirmed by comparing A2AR KO-SCH with WT-SCH gene groups. The distinct striatal gene expression profiles induced by A2AR KO and SCH should provide clues to the molecular mechanisms underlying the different phenotypes observed after genetic and pharmacological inactivation of A2AR. Furthermore, bioinformatics analysis discovered that Egr-2 binding sites were statistically overrepresented in the proximal promoters of A2AR KO-affected genes relative to the unaffected genes. This finding was further substantiated by the demonstration that the Egr-2 mRNA level increased in the striatum of both A2AR KO and SCH-treated mice and that striatal Egr-2 binding activity in the promoters of two A2AR KO-affected genes was enhanced in A2AR KO mice as assayed by chromatin immunoprecipitation. Taken together, these results strongly support the existence of an Egr-2-directed transcriptional regulatory network controlled by striatal A2ARs.   PUBMED: 16046619
Ontological Annotations:
  • D047369: Chromatin Immunoprecipitation (Publication, NCBO Annotator; PubMed MeSH Annotations)
  • D020411: Oligonucleotide Array Sequence Analysis (PubMed MeSH Annotations)
  • D018345: Mice, Knockout (PubMed MeSH Annotations)
  • MA:0000891: striatum (Publication, NCBO Annotator)
  • D000818: Animals (PubMed MeSH Annotations)
  • D051767: Early Growth Response Protein 2 (PubMed MeSH Annotations)
  • D015233: Models, Statistical (PubMed MeSH Annotations)
  • D008810: Mice, Inbred C57BL (PubMed MeSH Annotations)
  • D047468: Immunoprecipitation (Publication, NCBO Annotator)
  • D011401: Promoter Regions, Genetic (PubMed MeSH Annotations)
  • D002843: Chromatin (Publication, NCBO Annotator)
  • D004364: Pharmaceutical Preparations (Publication, NCBO Annotator)
  • D015536: Down-Regulation (Publication, NCBO Annotator; PubMed MeSH Annotations)
  • D043705: Receptor, Adenosine A2A (Publication, NCBO Annotator)
  • D005786: Gene Expression Regulation (PubMed MeSH Annotations)
  • D019295: Computational Biology (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D010641: Phenotype (PubMed MeSH Annotations)
  • D001665: Binding Sites (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D005190: Family (Publication, NCBO Annotator)
  • D013997: Time Factors (PubMed MeSH Annotations)
  • D001519: Behavior (Publication, NCBO Annotator)
  • D008954: Models, Biological (PubMed MeSH Annotations)
  • D014677: Pharmaceutical Vehicles (Publication, NCBO Annotator)
  • D014230: Triazoles (PubMed MeSH Annotations)
  • D016133: Polymerase Chain Reaction (PubMed MeSH Annotations)
  • D011743: Pyrimidines (PubMed MeSH Annotations)
  • D012333: RNA, Messenger (Publication, NCBO Annotator)
  • D043683: Receptors, Adenosine A2 (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • MP:0002169: no abnormal phenotype detected (Publication, NCBO Annotator)
  • GO:0000785: chromatin (Publication, NCBO Annotator)
  • D000241: Adenosine (Publication, NCBO Annotator)
  • GO:0005488: binding (Publication, NCBO Annotator)
  • D051379: Mice (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D015854: Up-Regulation (PubMed MeSH Annotations)
  • D013812: Therapeutics (Publication, NCBO Annotator)
  • GO:0010467: gene expression (Publication, NCBO Annotator)
  • D014158: Transcription, Genetic (PubMed MeSH Annotations)
  • D020869: Gene Expression Profiling (Publication, NCBO Annotator)

4 GeneSets from this Publication:


Select gene sets below using the check boxes, and then add them to a project using the pull down below. You can also create a project using the pull down. To view a set, click on the GeneSetID:GeneSet Description shown in green below.
GS86605: Table 1: Comparison of striatal gene expression by microarray and qPCR analyses A. KO-VEH vs. WT-VEH [DRG] provisional
GS86699: Table 1: Comparison of striatal gene expression by microarray and qPCR analyses D. KO-SCH vs. KO-VEH [DRG] provisional
GS87175: Table 1: Comparison of striatal gene expression by microarray and qPCR analyses B. WT-SCH vs. WT-VEH [DRG] provisional
GS87190: Table 1: Comparison of striatal gene expression by microarray and qPCR analyses C. KO-SCH vs. WT-SCH [DRG] provisional


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