ArticleJournal of neuroscience research2007
5'UTR of the neurogenic bHLH Nex1/MATH-2/NeuroD6 gene is regulated by two distinct promoters through CRE and C/EBP binding sites.
Article in Journal of neuroscience research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 20 citations in OpenAlex.
- DNA methylation of the promoter region at the CREB1 binding site is a mechanism for the epigenetic regulation of brain-specific PKMζ.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Article
- Epigenetic modifiers promote mitochondrial biogenesis and oxidative metabolism leading to enhanced differentiation of neuroprogenitor cells.Cell death & disease · 2018Article
- Nuclear factor kappa B signaling initiates early differentiation of neural stem cells.Stem cells (Dayton, Ohio) · 2012Article
- Autoregulation of co-chaperone BAG3 gene transcription.Journal of cellular biochemistry · 2009Article
- Cloning and characterization of the 5'UTR of the rat anti-apoptotic Bcl-w gene.Biochemical and biophysical research communications · 2009Article
- Angiopoietin 2 mediates the differentiation and migration of neural progenitor cells in the subventricular zone after stroke.The Journal of biological chemistry · 2009Article
- Identification of neuronal target genes for CCAAT/enhancer binding proteins.Molecular and cellular neurosciences · 2009Article
- Characterization of the proneural gene regulatory network during mouse telencephalon development.BMC biology · 2008Article
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Expression of the bHLH transcription factor Nex1/MATH-2/NeuroD6, a member of the NeuroD subfamily, parallels overt neuronal differentiation and synaptogenesis during brain development. Our previous studies have shown that Nex1 is a critical effector of the NGF pathway and promotes neuronal differentiation and survival of PC12 cells in the absence of growth factors. In this study, we investigated the transcriptional regulation of the Nex1 gene during NGF-induced neuronal differentiation. We found that Nex1 expression is under the control of two conserved promoters, Nex1-P1 and Nex1-P2, located in two distinct non-coding exons. Both promoters are TATA-less with multiple transcription start sites, and are activated on NGF or cAMP exposure. Luciferase-reporter assays showed that the Nex1-P2 promoter activity is stronger than the Nex1-P1 promoter activity, which supports the previously reported differential expression levels of Nex1 transcripts throughout brain development. Using a combination of DNaseI footprinting, EMSA assays, and site-directed mutagenesis, we identified the essential regulatory elements within the first 2 kb of the Nex1 5'UTR. The Nex1-P1 promoter is mainly regulated by a conserved CRE element, whereas the Nex1-P2 promoter is under the control of a conserved C/EBP binding site. Overexpression of wild-type C/EBPbeta resulted in increased Nex1-P2 promoter activity in NGF-differentiated PC12 cells. The fact that Nex1 is a target gene of C/EBPbeta provides new insight into the C/EBP transcriptional cascade known to promote neurogenesis, while repressing gliogenesis.
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