A common silencer element in the SCG10 and type II Na+ channel genes binds a factor present in nonneuronal cells but not in neuronal cells

Mori, Nozomu; Schoenherr, Christopher J.; Vandenbergh, David J.; Anderson, David J.

doi:10.1016/0896-6273(92)90219-4

Cited by 403 publications

(236 citation statements)

References 44 publications

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“…NRSF\REST was originally identified as a silencer-binding protein for the neuron-specific sodium channel gene (SCG10) [130], which binds to a conserved element known as NRSE [130,131] and was simultaneously cloned in separate studies [132,133]. NRSF\REST is known to be a 116 kDa protein [133] containing eight non-canonical zinc fingers [132], only one of which has been shown to be crucial for repression of the type II sodium channel gene [134].…”

Section: Nrsf/nrsementioning

confidence: 99%

“…NRSF\REST is known to be a 116 kDa protein [133] containing eight non-canonical zinc fingers [132], only one of which has been shown to be crucial for repression of the type II sodium channel gene [134]. Interestingly, several research groups have now identified NRSE-directed silencer activity in a variety of neuronal as well as non-neuronal genes [130][131][132][135][136][137][138][139][140][141].…”

Section: Nrsf/nrsementioning

confidence: 99%

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Transcriptional control and the role of silencers in transcriptional regulation in eukaryotes

Ogbourne

Antalis

1998

Biochemical Journal

223

171

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Mechanisms controlling transcription and its regulation are fundamental to our understanding of molecular biology and, ultimately, cellular biology. Our knowledge of transcription initiation and integral factors such as RNA polymerase is considerable, and more recently our understanding of the involvement of enhancers and complexes such as holoenzyme and mediator has increased dramatically. However, an understanding of transcriptional repression is also essential for a complete understanding of promoter structure and the regulation of gene expression. Transcriptional repression in eukaryotes is achieved through ‘silencers ’, of which there are two types, namely ‘silencer elements ’ and ‘negative regulatory elements ’ (NREs). Silencer elements are classical, position-independent elements that direct an active repression mechanism, and NREs are position-dependent elements that direct a passive repression mechanism. In addition, ‘repressors ’ are DNA-binding trasncription factors that interact directly with silencers. A review of the recent literature reveals that it is the silencer itself and its context within a given promoter, rather than the interacting repressor, that determines the mechanism of repression. Silencers form an intrinsic part of many eukaryotic promoters and, consequently, knowledge of their interactive role with enchancers and other transcriptional elements is essential for our understanding of gene regulation in eukaryotes.

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Section: Nrsf/nrsementioning

confidence: 99%

Section: Nrsf/nrsementioning

confidence: 99%

Transcriptional control and the role of silencers in transcriptional regulation in eukaryotes

Ogbourne

Antalis

1998

Biochemical Journal

223

171

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“…23 The NRSE is bound by the neuronal-restrictive silencer factor (NRSF) and functions to repress neuronal gene expression in non-neuronal tissues. 24 Two tandem copies of the NRSE element from either the rat SCG10, 25 or mouse n(AchR) 26,27 promoter were cloned either upstream or downstream of the INSM1 promoter region. Another modification analyzed was incorporation of the 18 bp neuronal and endocrine-specific enhancer element derived from the rat CT/CGRP gene promoter that is bound by a basic helix loop helix and OB2 octamer-binding protein complex, and termed the H/O enhancer.…”

Section: Resultsmentioning

confidence: 99%

Modifications to the INSM1 promoter to preserve specificity and activity for use in adenoviral gene therapy of neuroendocrine carcinomas

et al. 2012

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The INSM1 gene encodes a transcriptional repressor that is exclusively expressed in neuronal and neuroendocrine tissue during embryonic development that is re-activated in neuroendocrine tumors. Using the 1.7 kbp INSM1 promoter, an adenoviral HSV thymidine kinase gene therapy was tested for the treatment of neuroendocrine tumors. An unforeseen interference on the INSM1 promoter specificity from the adenoviral genome was observed. Attempts were made to protect the INSM1 promoter from the influence of essential adenoviral sequences and to further enhance the tissue specificity of the INSM1 promoter region. Using the chicken b-globin HS4 insulator sequence, we eliminated off-target tissue expression from the Ad-INSM1 promoter-luciferase2 constructs in vivo. In addition, inclusion of two copies of the mouse nicotinic acetylcholine receptor (n(AchR)) neuronal-restrictive silencer element (NRSE) reduced nonspecific activation of the INSM1 promoter both in vitro and in vivo. Further, inclusion of both the HS4 insulator with the n(AchR) 2 Â NRSE modification showed a two log increase in luciferase activity measured from the NCI-H1155 xenograft tumors compared with the original adenovirus construct. The alterations increase the therapeutic potential of adenoviral INSM1 promoter-driven suicide gene therapy for the treatment of a variety of neuroendocrine tumors.

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“…REST, also known as NRSF or X box repressor (XBR), is the first identified system-wide transcription repressor implicated in vertebrate neuronal development [4,[24][25][26][27] . However, more and more studies have provided evidence that REST plays an essential role in non-neuronal tissues [28] by functioning as a transcription silencer or activator [29][30][31][32][33][34] .…”

Section: Discussionmentioning

confidence: 99%

Involvement of REST corepressor 3 in prognosis of human hepatitis B

Xue

Zheng

et al. 2011

Acta Pharmacol Sin

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Aim: To examine the potential correlation between serum REST corepressor 3 (RCOR3) level and the outcome of patients with hepatitis B. Methods: Concanavalin A (ConA)-induced mouse hepatitis model was used. The mRNA level of RCOR3 in mouse liver was measured using GeneChip array and real-time PCR. One hundred seventy-seven patients with hepatitis B and 34 healthy individuals were categorized into six groups including mild chronic hepatitis, moderate chronic hepatitis B, severe hepatitis B (SHB), cirrhosis, hepatocellular carcinoma (HCC) and healthy control. Serum levels of human RCOR3 were measured using ELISA. Results: In the mouse hepatitis model, the mRNA level of RCOR3 in liver was reduced early after exposure to ConA, then increased after 6 h of exposure. There was no significant difference in the serum RCOR3 level between the mild chronic hepatitis B and the control groups. The serum RCOR3 level was significantly increased in the moderate chronic hepatitis B group, but significantly reduced in SHB, cirrhosis and HCC groups, as compared with the control group. Moreover, the serum RCOR3 levels in SHB, cirrhosis and liver cancer patients were significantly lower than those in the patients with moderate chronic hepatitis B and with mild chronic hepatitis B. Rank correlation analysis revealed a significant correlation between serum RCOR3 level and total bilirubin (r=-0.305, P<0.01). There was no significant correlation between RCOR3 on one hand, and alanine transaminase (r=0.014, P>0.05) or aspartate transaminase (r=-0.079, P>0.05) on the other hand. Conclusion: Serum RCOR3 level may reflect the degree of liver damage, which might be a potential biomarker for the outcome of patients with hepatitis B.

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A common silencer element in the SCG10 and type II Na+ channel genes binds a factor present in nonneuronal cells but not in neuronal cells

Cited by 403 publications

References 44 publications

Transcriptional control and the role of silencers in transcriptional regulation in eukaryotes

Transcriptional control and the role of silencers in transcriptional regulation in eukaryotes

Modifications to the INSM1 promoter to preserve specificity and activity for use in adenoviral gene therapy of neuroendocrine carcinomas

Involvement of REST corepressor 3 in prognosis of human hepatitis B

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