ArticleProceedings of the National Academy of Sciences of the United States of America1998
Identification of a neuregulin and protein-tyrosine phosphatase response element in the nicotinic acetylcholine receptor epsilon subunit gene: regulatory role of an Rts transcription factor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 60 citations in OpenAlex.
- A Truncating Variant ofJournal of pediatric genetics · 2022Article
- Gene Expression Profile at the Motor Endplate of the Neuromuscular Junction of Fast-Twitch Muscle.Frontiers in molecular neuroscience · 2020Article
- Ets-2 is involved in transcriptional regulation of C1qTNF-related protein 5 in muscle cells.Molecular biology reports · 2012Article
- Molecular control of neuromuscular junction development.Journal of cachexia, sarcopenia and muscle · 2012Article
- Chromatin modifications that support acetylcholine receptor gene activation are established during muscle cell determination and differentiation.Molecular biology reports · 2011Article
- hnRNP H enhances skipping of a nonfunctional exon P3A in CHRNA1 and a mutation disrupting its binding causes congenital myasthenic syndrome.Human molecular genetics · 2008Article
- Ets-2 repressor factor silences extrasynaptic utrophin by N-box mediated repression in skeletal muscle.Molecular biology of the cell · 2007Article
- Inhibition of MuSK expression by CREB interacting with a CRE-like element and MyoD.Molecular and cellular biology · 2005Article
- Expression of mutant Ets protein at the neuromuscular synapse causes alterations in morphology and gene expression.EMBO reports · 2002Article
- The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia.BMC psychiatry · 2002Article
- Sodium channel mRNAs at the neuromuscular junction: distinct patterns of accumulation and effects of muscle activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2001Article
- Ets target genes: past, present and future.Oncogene · 2000Review
- The Agrin/MuSK signaling pathway is spatially segregated from the neuregulin/ErbB receptor signaling pathway at the neuromuscular junction.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2000Article
- The Ets transcription factor GABP is required for postsynaptic differentiation in vivo.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2000Article
- The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses.Proceedings of the National Academy of Sciences of the United States of America · 2000Article
- Regulation of neuregulin-mediated acetylcholine receptor synthesis by protein tyrosine phosphatase SHP2.The Journal of neuroscience : the official journal of the Society for Neuroscience · 1999Article
- Essential roles of c-JUN and c-JUN N-terminal kinase (JNK) in neuregulin-increased expression of the acetylcholine receptor epsilon-subunit.The Journal of neuroscience : the official journal of the Society for Neuroscience · 1999Article
- Activation of utrophin promoter by heregulin via the ets-related transcription factor complex GA-binding protein alpha/beta.Molecular biology of the cell · 1999Article
- An intronic enhancer containing an N-box motif is required for synapse- and tissue-specific expression of the acetylcholinesterase gene in skeletal muscle fibers.Proceedings of the National Academy of Sciences of the United States of America · 1999Article
- Induction of utrophin gene expression by heregulin in skeletal muscle cells: role of the N-box motif and GA binding protein.Proceedings of the National Academy of Sciences of the United States of America · 1999Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
At the neuromuscular synapse, innervation induces endplate-specific expression of adult-type nicotinic acetylcholine receptors by selective expression of their subunit-encoding genes (alpha2betaepsilondelta) in endplate-associated myonuclei. These genes are specifically regulated by protein-tyrosine phosphatase (PTPase) activity. In addition, neuregulin/acetylcholine-receptor-inducing activity, a nerve-derived factor that stimulates nicotinic acetylcholine receptor synthesis, induces adult-type specific epsilon subunit gene expression via activation of a Ras/mitogen-activated protein kinase pathway. However, the DNA regulatory elements and the binding proteins that mediate PTPase and neuregulin-dependent gene expression remain unknown. Herein we report that PTPase, neuregulin, and Ras-dependent regulation of the epsilon subunit gene map to a 15-bp promoter sequence. Interestingly, this same 15-bp sequence appears to be necessary for low epsilon subunit gene expression in extrajunctional regions of the muscle fiber. Site-directed mutagenesis of a putative Ets binding site located within this 15-bp sequence, reduced PTPase, neuregulin, and Ras-dependent regulation. Overexpression of the rat muscle Ets-2 transcription factor resulted in a sequence-specific induction of epsilon subunit promoter activity. Further, a dominant negative mutant of Ets-2 abolished neuregulin-dependent induction of epsilon subunit gene expression. Thus, these results indicate a crucial role for the 15-bp element in determining synapse-specific and neuregulin-mediated motor neuron control of epsilon subunit gene expression and suggest the participation of Ets transcription factor(s) in this control.
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