RRC ID 28620
Author Tanaka S, Kodama T, Nonaka T, Toyoda H, Arai M, Fukazawa M, Honda Y, Honda M, Mignot E.
Title Transcriptional regulation of the hypocretin/orexin gene by NR6A1.
Journal Biochem. Biophys. Res. Commun.
Abstract The hypocretin (also known as orexin) neuropeptide system coordinates the regulation of various physiological processes. A reduction in Nr6a1 expression was observed in hypocretin neuron-ablated transgenic mice. To show that prepro-hypocretin transcription is functionally modulated by NR6A1, we performed chromatin immunoprecipitation (ChIP) analysis, double-immunostaining, a luciferase reporter assay, and an in utero electroporation study. ChIP analysis showed that endogenous NR6A1 binds to a putative NR6A1-binding site. Double-immunostaining indicated almost all hypocretin neurons were positive for NR6A1 immunoreactivity. NR6A1 overexpression in SH-SY5Y cells modulated hypocretin promoter activity, an effect that was countered by lacking a putative NR6A1-binding site. Electroporation with Nr6a1 in the foetal hypothalamus promoted hypocretin transcription as compared to GFP-electroporation. These experiments confirmed that NR6A1 works as a regulator for hypocretin transcription.
Volume 403(2)
Pages 178-83
Published 2010-12-10
DOI 10.1016/j.bbrc.2010.11.001
PII S0006-291X(10)02033-4
PMID 21056546
PMC PMC3012206
MeSH Animals Base Sequence Cell Line DNA Mutational Analysis Gene Expression Regulation* Humans Hypothalamus / metabolism Immunoprecipitation Intracellular Signaling Peptides and Proteins / genetics* Male Mice Mice, Inbred C57BL Molecular Sequence Data Neuropeptides / genetics* Nuclear Receptor Subfamily 6, Group A, Member 1 / metabolism* Orexins Promoter Regions, Genetic Sequence Deletion Transcription, Genetic
IF 2.705
Times Cited 9
DNA material pCAG-mNr6a1 (RDB08376) NR6A1/TNT (RDB08377)