Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mammalian HES1 and HES5 are abundant in developing CNS and inhibit neurogenesis, while HES6 promotes neurogenesis. An early serotonergic differentiation marker, the 5-HT1A receptor, is repressed by HES5 and DEAF1 which recognize the C(-1019), but not G(-1019) allele of a human 5-HT1A promoter polymorphism associated with mood disorders. We tested whether HES1 and HES6 regulate transcriptional activity at this element. HES1 strongly repressed 5-HT1A transcription in neuronal and non-neuronal cells, while HES6 reversed HES1- and HES5-mediated repression. Mutation of a putative HES consensus site blocked HES1 and HES5, but, unlike HES5, HES1 repressed at the G(-1019) allele. To address its role in vivo, the temporal expression of 5-HT1A receptor RNA and protein was examined in HES1-/- mice, and elevated levels in E12.5 hindbrain and midbrain were observed. Thus, HES1 and HES6 oppositely regulate 5-HT1A receptor transcription and HES1 is required for its correct developmental expression.
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PMID:HES1 regulates 5-HT1A receptor gene transcription at a functional polymorphism: essential role in developmental expression. 1849 74