The early response gene NGFI-C encodes a zinc finger transcriptional activator and is a member of the GCGGGGGCG (GSG) element-binding protein family.

Crosby, Seth D.; Puetz, John; Simburger, Kelli S.; Fahrner, Timothy J.; Milbrandt, Jeffrey

doi:10.1128/mcb.11.8.3835

Cited by 180 publications

(112 citation statements)

References 51 publications

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“…Increased levels of pup LG enhance hippocampal expression of GR mRNA splice variants containing exon 1 7 [45], suggesting greater transcriptional activity through this promoter. The exon 1 7 sequence contains an NGFI-A response element [49,50]. Pup LG increases hippocampal NGFI-A expression and chromatin immunoprecipitation (ChIP) assays, which permit quantification of protein interactions with specific DNA sequences, with hippocampal samples reveal increased NGFI-A association with the exon 1 7 promoter in pups of High compared with Low LG mothers [45].…”

Section: Molecular Transduction Of Parental Signalsmentioning

confidence: 99%

Environmental regulation of the neural epigenome

et al. 2011

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a b s t r a c tParental effects are a major source of phenotypic plasticity. Moreover, there is evidence from studies with a wide range of species that the relevant parental signals are influenced by the quality of the parental environment. The link between the quality of the environment and the nature of the parental signal is consistent with the idea that parental effects, whether direct or indirect, might serve to influence the phenotype of the offspring in a manner that is consistent with the prevailing environmental demands. In this review we explore recent studies from the field of 'environmental epigenetics' that suggest that (1) DNA methylation states are far more variable than once thought and that, at least within specific regions of the genome, there is evidence for both demethylation and remethylation in post-mitotic cells and (2) that such remodeling of DNA methylation can occur in response to environmentally-driven, intracellular signaling pathways. Thus, studies of variation in mother-offspring interactions in rodents suggest that parental signals operate during pre-and/ or post-natal life to influence the DNA methylation state at specific regions of the genome leading to sustained changes in gene expression and function. We suggest that DNA methylation is a candidate mechanism for parental effects on phenotypic variation.

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Section: Molecular Transduction Of Parental Signalsmentioning

confidence: 99%

Environmental regulation of the neural epigenome

et al. 2011

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“…pLuc 135/ Egr-1 mut reporter plasmid was constructed by introducing point mutations known to abolish Egr-1 binding (Crosby et al, 1991) into the core sequence (CGGGG to CTAGG) of each of the two potential Egr-1 binding sites within the 785 to 750 region. In reporter plasmid pLuc 135/Sp1 mut mutations known to abolish Sp1 binding (GGGCGG to GTTCGG;Anderson and Freytag, 1991) were introduced into each of the three potential Sp1 binding sites ( Figure 4a).…”

Section: Identi®cation Of Sequences From the 5'-¯anking Region Of Thementioning

confidence: 99%

Sp1 recognition sites in the proximal promoter of the human vascular endothelial growth factor gene are essential for platelet-derived growth factor-induced gene expression

Finkenzeller

Sparacio

Technau³

et al. 1997

Oncogene

182

170

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Stimulation of NIH3T3 cells with platelet-derived growth factor (PDGF)-BB enhances expression of vascular endothelial growth factor (VEGF), an endothelial cell-speci®c mitogen and a key mediator of tumor angiogenesis. Here, we identi®ed cis-acting VEGF promoter elements and trans-acting factors which are involved in PDGF-stimulated VEGF expression. By 5'-deletion and transient transfection analysis, a G+C-rich region at 785 to 750 of the human VEGF promoter was shown to be necessary and su cient for both PDGF inducible and basal expression. The region contains three potential recognition sites for Sp1 transcription factors, which overlap with two Egr-1 sites. Mutations that abolish the ability of Sp1 to interact with the VEGF promoter element also abrogate expression induced by PDGF. Mutations of the potential Egr-1 binding sites did not a ect PDGF responsiveness. Gel shift and antibody supershift analyses showed that Sp1 and Sp3 interact constitutively with the VEGF promoter element. Our data strongly suggest that enhanced VEGF gene expression in PDGF-induced NIH3T3 cells is mediated by Sp1 and/or Sp3 transcription factors bound to the 785 to 750 promoter region of the VEGF gene.

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“…The NGFI-A cDNA was cut at its BglII site and ligated into the BamHI site of pATH1, resulting in a small truncation (residues 1 to 15) of the full-length sequence. The NGFI-C expression construct was described previously (11). Fulllength Egr3 and Krox20 were amplified by PCR (using cDNA made from serumstarved and then serum-cycloheximide-induced NRK cells as a template), verified by partial sequencing, and ligated into the EcoRI site of pATH1.…”

Section: Methodsmentioning

confidence: 99%

“…Fulllength Egr3 and Krox20 were amplified by PCR (using cDNA made from serumstarved and then serum-cycloheximide-induced NRK cells as a template), verified by partial sequencing, and ligated into the EcoRI site of pATH1. Protein expression was induced in Escherichia coli DH5␣ cells (GIBCO-BRL) and solubilized for separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) as described previously (11,18). Proteins used in all gel shift experiments were synthesized by in vitro-coupled transcription and translation by using the TnT system (Promega).…”

Section: Methodsmentioning

confidence: 99%

DNA-Binding Specificity of NGFI-A and Related Zinc Finger Transcription Factors

Swirnoff

Milbrandt

1995

Molecular and Cellular Biology

Self Cite

299

287

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NGFI-A is the prototypic member of a family of immediate-early gene-encoded transcription factors which includes NGFI-C, Egr3, and Krox20. These proteins possess highly homologous DNA-binding domains, composed of three Cys 2 -His 2 zinc fingers, and all bind to and activate transcription from the sequence GCGGGGGCG. We used a PCR-mediated random site selection protocol to determine whether other sites could be bound by these proteins and the extent to which their binding site preferences are similar or different. The high-affinity consensus sites generated from the selection data are similar, and the combined consensus sequence is T -G-C-G-T/g-G/A-G-G-C/a/t-G-G/T (lowercase letters indicate bases selected less frequently).Using gel shift assays, we found that sequences that diverge from the consensus were bound by NGFI-A, confirming that there is greater variability in binding sites than has generally been acknowledged. We also provide evidence that protein-DNA interactions not noted, or whose importance was not apparent from the X-ray cocrystal structure of the NGFI-A zinc fingers complexed with DNA, contribute significantly to the binding energy of these proteins and confirm that an optimal site is at least 10 instead of 9 nucleotides in length. In contrast to the similarities in binding specificity among these proteins, we found that while NGFI-A, Egr3, and Krox20 have comparable DNA binding affinities and kinetics of dissociation, the affinity of NGFI-C is more than threefold lower. This could result in differential regulation of target genes in cells where NGFI-C and the other proteins are coexpressed. Furthermore, we show that this affinity difference is a property not of the zinc fingers themselves but rather of the protein context of the DNA-binding domain.

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The early response gene NGFI-C encodes a zinc finger transcriptional activator and is a member of the GCGGGGGCG (GSG) element-binding protein family.

Cited by 180 publications

References 51 publications

Environmental regulation of the neural epigenome

Environmental regulation of the neural epigenome

Sp1 recognition sites in the proximal promoter of the human vascular endothelial growth factor gene are essential for platelet-derived growth factor-induced gene expression

DNA-Binding Specificity of NGFI-A and Related Zinc Finger Transcription Factors

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