The EGR family of transcription-regulatory factors: progress at the interface of molecular and systems neuroscience

O’Donovan, Kevin J.; Tourtellotte, Warren G.; Millbrandt, Jeffrey; Baraban, Jay M.

doi:10.1016/s0166-2236(98)01343-5

Cited by 418 publications

(316 citation statements)

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“…Egr3 expression is mitogenically induced in fibroblasts (Patwardhan et al, 1991) and is upregulated by electroconvulsive stimulation in hippocampal granule cells and other neuronal activity (O'Donovan et al, 1998), but the role of regulation by growth factors in cell types other than neurons or T cells has not previously been widely investigated. The discovery that transcriptional regulators, such as the NGFI-A-binding proteins called NABs, can suppress Egr-mediated mRNA expression suggests that changes in Egr3 mRNA levels are not the only determinant of transcriptional activation dependent on this factor (O'Donovan et al, 1999). However, VEGF-induced Egr transcriptional activation and both Egr3 mRNA upregulation and transcriptional activation were blocked by specific inhibitors of KDR, PKC and ERK pathway, indicating that the same signalling pathway mediated these responses.…”

Section: Discussionmentioning

confidence: 99%

“…The Egr family comprises four members, Egr1, Egr2, Egr3 and Egr4, all characterized by a highly conserved DNA-binding domain composed of three Cys2-His2 zinc-finger motifs recognizing a nine-base-pair segment of DNA (GCGGGGGCG), with each finger spanning three nucleotides (O'Donovan et al, 1999). Egr1, -2 and -3 are transcriptional activators, whereas Egr4 is a transcriptional repressor.…”

Section: Introductionmentioning

confidence: 99%

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The zinc-finger transcription factor, early growth response 3, mediates VEGF-induced angiogenesis

et al. 2007

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The zinc-finger transcription factor, early growth response 3, mediates VEGF-induced angiogenesis

et al. 2007

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“…The early growth response (Egr) family of transcription factors was initially discovered as genes up-regulated in response to growth factors [1]. There are four known family members, each of which contains a highly conserved zinc finger DNA binding domain.…”

Section: Introductionmentioning

confidence: 99%

Opposing regulation of T cell function by Egr‐1/NAB2 and Egr‐2/Egr‐3

et al. 2008

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TCR-induced NF-AT activation leads to the up-regulation of multiple genes involved in T cell anergy. Since NF-AT is also involved in T cell activation, we have endeavored to dissect TCR-induced activating and inhibitory genetic programs. This approach revealed roles for the early growth response (Egr) family of transcription factors and the Egr coactivator/corepressor NGFI-A-binding protein (NAB)2 in regulating T cell function. TCR-induced Egr-1 and NAB2 enhance T cell function, while Egr-2 and Egr-3 inhibit T cell function. In this report, we demonstrate that Egr-2 and Egr-3 are induced by NF-AT in the absence of AP-1, while Egr-1 and NAB2 both require AP-1-mediated transcription. Our data suggest that Egr-3 is upstream of Egr-2, and that mechanistically Egr-2 and Egr-3 suppress Egr-1 and NAB2 expression. Functionally, T cells from Egr-2 and Egr-3 null mice are hyperresponsive while T cells from Egr-3 transgenic, overexpressing mice are hyporesponsive. Furthermore, an in vivo model of autoimmune pneumonitis reveals that T cells from Egr-3 null mice hasten death while Egr-3-overexpressing T cells cause less disease. Overall, our data suggest that just as the Egr/NAB network of genes control cell fate in other systems, TCR-induced Egr-1, 2, 3 and NAB2 control the fate of antigen recognition in T cells.

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“…The rationale for using both Egr-1 and c-fos in the present study was due to the different induction pathways of these genes, as well as the fact that basal Egr-1 expression has been demonstrated to be under noradrenergic control (O'Donovan et al, 1999). Therefore, given the study of serotonergic and noradrenergic antidepressants, we determined to study if there would be similar or differential induction of c-fos and Egr-1 mRNA.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Alterations in c-fos and Egr-1 (zif268) Expression Throughout the Rat Brain Following Acute Administration of Different Classes of Antidepressant Compounds

Slattery

Morrow²,

Hudson

et al. 2005

Neuropsychopharmacol

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The majority of immediate-early gene (IEG) studies focus on a few key brain regions associated with the class of psychoactive compound being studied. Recently, using a meta-analysis of the c-fos literature, we demonstrated the utility of c-fos profiling to classify such compounds. The present study examined acute delivery of a range of antidepressant classes; fluoxetine, imipramine, LiCl, and mirtazapine. The dual aims were to study the IEG profiles of these varying classes of antidepressants throughout the rat brain and to compare the utility of c-fos or Egr-1 as IEGs to classify clinically efficacious antidepressants. All antidepressants increased c-fos mRNA in the central amygdala, as previously shown, while c-fos was also increased in the anterior insular cortex and significantly decreased within the septum. Although acute antidepressant administration altered c-fos expression in a number of brain regions, Egr-1 expression was only significantly altered in the central amygdala, suggesting that Egr-1 may not be as useful a marker to investigate acute antidepressant treatment. The fact that these drugs, including the previously unclassified antidepressant mirtazapine, share a number of common loci of activation, which are implicated by human and animal studies in depression, adds further support to the use of IEG mapping to classify psychoactive compounds.

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The EGR family of transcription-regulatory factors: progress at the interface of molecular and systems neuroscience

Cited by 418 publications

References 50 publications

The zinc-finger transcription factor, early growth response 3, mediates VEGF-induced angiogenesis

The zinc-finger transcription factor, early growth response 3, mediates VEGF-induced angiogenesis

Opposing regulation of T cell function by Egr‐1/NAB2 and Egr‐2/Egr‐3

Comparison of Alterations in c-fos and Egr-1 (zif268) Expression Throughout the Rat Brain Following Acute Administration of Different Classes of Antidepressant Compounds

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