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Publication : Molecular characterization of a rat negative regulator with a basic helix-loop-helix structure predominantly expressed in the developing nervous system.

First Author  Akazawa C Year  1992
Journal  J Biol Chem Volume  267
Issue  30 Pages  21879-85
PubMed ID  1400497 Mgi Jnum  J:71335
Mgi Id  MGI:2149691 Doi  10.1016/s0021-9258(19)36694-3
Citation  Akazawa C, et al. (1992) Molecular characterization of a rat negative regulator with a basic helix-loop-helix structure predominantly expressed in the developing nervous system. J Biol Chem 267(30):21879-85
abstractText  We report here the cDNA cloning and characterization of a rat basic helix-loop-helix (HLH) factor, designated HES-5. This factor has a distant sequence homology to Drosophila hairy and Enhancer-of-split proteins, both of which are required for normal neurogenesis. DNase I footprinting analyses show that HES-5 binds to the sequence CACNAG (called N box), a recognition sequence of Enhancer-of-split proteins. Although HES-5 does not bind to the sequence CANNTG (called E box) recognized by other HLH factors, it attenuates the binding of E47, an HLH activator, to E box by forming a hetero-oligomer. In cotransfection analyses using NIH 3T3 cells, HES-5 significantly represses transcription originating from the promoter containing the N box sequences. Furthermore, HES-5 also partially inhibits the E47-induced expression from the promoter containing E boxes. Northern blot, RNase protection, and in situ hybridization analyses demonstrate that the HES-5 mRNA is specifically expressed in the nervous system. Prominent expression is observed in the ventricular zones of the embryonal brain vesicles and the outer nuclear layer of the neural retina. These results suggest that the negative regulator HES-5 may play an important role in neural development.
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