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.
journal_name
Neuroreportjournal_title
Neuroreportauthors
Moon SM,Kim JS,Park BR,Kim DK,Kim SG,Kim HJ,Chun HS,Lee BK,Kim CSdoi
10.1097/WNR.0000000000000316subject
Has Abstractpub_date
2015-02-11 00:00:00pages
144-51issue
3eissn
0959-4965issn
1473-558Xjournal_volume
26pub_type
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