| First Author | Jacobsen KX | Year | 2008 |
| Journal | Mol Cell Neurosci | Volume | 38 |
| Issue | 3 | Pages | 349-58 |
| PubMed ID | 18499474 | Mgi Jnum | J:137064 |
| Mgi Id | MGI:3797702 | Doi | 10.1016/j.mcn.2008.03.007 |
| Citation | Jacobsen KX, et al. (2008) HES1 regulates 5-HT1A receptor gene transcription at a functional polymorphism: essential role in developmental expression. Mol Cell Neurosci 38(3):349-58 |
| abstractText | 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. |
