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Ctbp2 should also be
considered a high priority biological candidate gene responsible for
modulating App expression levels. The C-terminal binding protein 2 is a
transcriptional co-repressor also known as Ribeye. The gene produces two transcripts encoding distinct
proteins. The short form is a transcriptional repressor that binds a
Pro-X-Asp-Leu-Ser peptide motif and interacts with several transcription
factors including EVI1, ZFPM1, and ZFHX1A (aka TCF8, deltaEF1). The longer
isoform is a major component of specialized synapses in photoreceptors. Both
proteins contain a NAD+ binding domain similar to NAD+-dependent
2-hydroxyacid dehydrogenases.
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Notes:
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1. To find out more about
CTBP2 protein and the Ctbp2 gene, link to iHOP at
http://www.pdg.cnb.uam.es/UniPub/iHOP/ and type in CTBP2
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Try Arrowsmith at
http://arrowsmith.psych.uic.edu/cgi-test/arrowsmith_uic/pubsmith.cgi
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2. Both APP and CTBP2 are
involved in oxidoreducatase activity or Notch signaling. To establish this
common gene ontology visit NCBI
http://www.ncbi.nih.gov/entrez/query.fcgi?db=gene and enter each gene
symbol.
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3. You can get
interesting hints regarding Ctbp2 expression partners by examining the
genetic correlations between Ctbp2 probe set 1422887_a_at and all other
transcripts on the M430 Affymetrix array. Use the Striatum data set because
we already know from previous work (the previous slide) that this gene is a
cis QTL. You should be able to
show that Ctbp2 and Notch3 have antagonistic expression patterns in
striatum. The negative genetic correlation with E2f4 is even stronger. The
transcript also has a high positive genetic correlation with Rdh14. Of
particular interest with respect to APP protein processing, Ctbp2 covaries
positively with Bace2 (the transcript of the beta site APP-cleaving enzyme
2).
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