Transcriptional regulation of the hypocretin/orexin gene by NR6A1 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Tanaka, S., Kodama, T., Nonaka, T., Toyoda, H., Arai, M., Fukazawa, M., Honda, Y., Honda, M., Mignot, E. 2010; 403 (2): 178-183


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.

View details for DOI 10.1016/j.bbrc.2010.11.001

View details for Web of Science ID 000285534500004

View details for PubMedID 21056546

View details for PubMedCentralID PMC3012206