title: Transcriptional regulation of the neuropeptide VGF by the neuron-restrictive silencer factor/neuron-restrictive silencer element.
abstract: The neurotrophin-inducible gene VGF plays an important role in the maintenance of organismal energy balance and in the mediation of hippocampal synaptic activity. The regulatory mechanism of VGF transcription is not fully understood. The neuron-restrictive silencer factor (NRSF) binds with the neuron-restrictive silencer element (NRSE), thereby suppressing the transcription of NRSE-containing genes. In this study, we show that the NRSE sequence of the VGF gene critically regulates the repression of VGF expression in NMB cells. Sequence analysis also establishes the presence of two putative NRSEs (NRSE-1 and NRSE-2) in the promoter region of the VGF gene. In reporter gene experiments, a more than eight-fold increase in the promoter activity was observed when both NRSE-1 and NRSE-2 were deleted. Deletion of NRSE-2 alone did not affect the promoter activity, thus indicating that NRSE-1 could be solely responsible for the repression of VGF gene expression. Mutations in the NRSE-1 sequence increased promoter activity. However, no change in activity was observed when NRSE-1 was coexpressed with dominant-negative NRSF, thereby suggesting that endogenous NRSF interacts with NRSE-1. Binding of NRSF to NRSE in a sequence-specific manner was confirmed with chromatin immunoprecipitation assays, respectively. Furthermore, the overexpressed NRSF in PC12 cells significantly suppressed the VGF gene expression by interacting with the NRSE located in the VGF promoter region. Our results indicate that NRSF plays an important role as a repressor of VGF gene regulation in NMB cells through a mechanism that is dependent on VGF-NRSE.
authors.affiliation: aSchool of Dentistry, Oral Biology Research Institute bDepartment of Biomedical Science cThe Division of Natural Medical Sciences, College of Health Science, Chosun University, Gwangju, Republic of Korea dDepartment of Microbiology, University of Tennessee, Knoxville, Tennessee, USA.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Moon
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Kim
authors.forename: Bo Ram
authors.initials: BR
authors.lastname: Park
authors.forename: Do Kyung
authors.initials: DK
authors.lastname: Kim
authors.forename: Su-Gwan
authors.initials: SG
authors.lastname: Kim
authors.forename: Heung-Joong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hong Sung
authors.initials: HS
authors.lastname: Chun
authors.forename: Byung-Kwon
authors.initials: BK
authors.lastname: Lee
authors.forename: Chun Sung
authors.initials: CS
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D009154:Mutation; D009414:Nerve Growth Factors / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D016716:PC12 Cells; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D000099229:RE1-Silencing Transcription Factor
chemical_list: D009414:Nerve Growth Factors; D009479:Neuropeptides; D012333:RNA, Messenger; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor; C510637:VGF protein, human; C062040:Vgf protein, rat