Factor binding and chromatin modification in the promoter of murine Egr1 gene upon induction

Tur, Gema; Georgieva, Elena; Gagete, Andrés P.; López-Rodas, Gerardo; Rodrı́guez, José Luis; Franco, Luís

doi:10.1007/s00018-010-0426-3

Cited by 31 publications

(50 citation statements)

References 44 publications

(74 reference statements)

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“…Previous studies of IEGs during serum stimulation in HCT116 cells have shown that their transcription is transient, with production leveling off or declining in 30 to 60 min, and that the mRNAs are short-lived (69)(70)(71)90). This response is a model of CDK8 regulation (41).…”

Section: Discussionmentioning

confidence: 90%

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Retroviral Cyclin Controls Cyclin-Dependent Kinase 8-Mediated Transcription Elongation and Reinitiation

Birkenheuer

Brewster

Quackenbush

et al. 2015

J Virol

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Walleye dermal sarcoma virus (WDSV) infection is associated with the seasonal development and regression of walleye dermal sarcoma. Previous work showed that the retroviral cyclin (RV-cyclin), encoded by WDSV, has separable cyclin box and transcription activation domains. It binds to cyclin-dependent kinase 8 (CDK8) and enhances its kinase activity. CDK8 is evolutionarily conserved and is frequently overexpressed in human cancers. It is normally activated by cyclin C and is required for transcription elongation of the serum response genes (immediate early genes [IEGs]) FOS, EGR1, and cJUN. The IEGs drive cell proliferation, and their expression is brief and highly regulated. Here we show that constitutive expression of RV-cyclin in the HCT116 colon cancer cell line significantly increases the level of IEG expression in response to serum stimulation. Quantitative reverse transcription-PCR (RT-PCR) and nuclear run-on assays provide evidence that RV-cyclin does not alter the initiation of IEG transcription but does enhance the overall rate of transcription elongation and maintains transcription reinitiation. RVcyclin does not increase activating phosphorylation events in the mitogen-activated protein kinase pathway and does not inhibit decay of IEG mRNAs. At the EGR1 gene locus, RV-cyclin increases and maintains RNA polymerase II (Pol II) occupancy after serum stimulation, in conjunction with increased and extended EGR1 gene expression. The RV-cyclin increases CDK8 occupancy at the EGR1 gene locus before and after serum stimulation. Both of RV-cyclin's functional domains, i.e., the cyclin box and the activation domain, are necessary for the overall enhancement of IEG expression. RV-cyclin presents a novel and ancient mechanism of retrovirus-induced oncogenesis. IMPORTANCEThe data reported here are important to both virology and cancer biology. The novel mechanism pinpoints CDK8 in the development of walleye dermal sarcoma and sheds light on CDK8's role in many human cancers. CDK8 controls expression from highly regulated genes, including the interferon-stimulated genes. Its function is likely the target of many viral interferon-resistance mechanisms. CDK8 also controls cellular responses to metabolic stimuli, stress, and hypoxia, in addition to the serum response. The retroviral cyclin (RV-cyclin) represents a highly selected probe of CDK8 function. RV-cyclin does not control CDK8 specificity but instead enhances CDK8's effects on regulated genes, an important distinction for its use to delineate natural CDK8 targets. The outcomes of this research are applicable to investigations of normal and abnormal CDK8 functions. The mechanisms defined here will contribute directly to the dermal sarcoma model in fish and clarify an important path for oncogenesis and innate resistance to viruses. T he complex retrovirus walleye dermal sarcoma virus (WDSV) is associated with the seasonal development and regression of dermal sarcoma in walleye fish (Sander vitreus) (1-7). The seasonal nature of the tumor is coupled with a...

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Section: Discussionmentioning

confidence: 90%

“…IEGs are transiently activated in a CDK8-dependent manner upon stimulation with serum (41,(67)(68)(69)(70). HCT116 cells were used to demonstrate CDK8 regulation of IEG expression (41).…”

Section: Fos Egr1mentioning

confidence: 99%

Retroviral Cyclin Controls Cyclin-Dependent Kinase 8-Mediated Transcription Elongation and Reinitiation

Birkenheuer

Brewster

Quackenbush

et al. 2015

J Virol

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“…ChIP experiments have shown that Srf is constitutively bound to serum response elements (SREs) at the Egr1 promoter that are essential for the activation of Egr1 by TCR signaling (Xi and Kersh 2003;Tur et al 2010). To determine whether Srf binding to Egr1 is dependent on Bptf, we performed ChIP on DN thymocytes and observed significant Bptf dependence for the occupancy of Srf at the promoter and the À5.9 kb upstream region (P-value < 0.05) (Fig.…”

Section: Bptf Is Required For Dna Binding Of Transcription Factors Immentioning

confidence: 99%

Chromatin remodeling complex NURF regulates thymocyte maturation

Landry

Banerjee²,

Taylor³

et al. 2011

Genes Dev.

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The maturation of T cells requires signaling from both cytokine and T-cell receptors to gene targets in chromatin, but how chromatin architecture influences this process is largely unknown. Here we show that thymocyte maturation post-positive selection is dependent on the nucleosome remodeling factor (NURF). Depletion of Bptf (bromodomain PHD finger transcription factor), the largest NURF subunit, in conditional mouse mutants results in developmental arrest beyond the CD4 + CD8 int stage without affecting cellular proliferation, cellular apoptosis, or coreceptor gene expression. In the Bptf mutant, specific subsets of genes important for thymocyte development show aberrant expression. We also observed defects in DNase I-hypersensitive chromatin structures at Egr1, a prototypical Bptf-dependent gene that is required for efficient thymocyte development. Moreover, chromatin binding of the sequence-specific factor Srf (serum response factor) to Egr1 regulatory sites is dependent on Bptf function. Physical interactions between NURF and Srf suggest a model in which Srf recruits NURF to facilitate transcription factor binding at Bptf-dependent genes. These findings provide evidence for causal connections between NURF, transcription factor occupancy, and gene regulation during thymocyte development.

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“…The activation of Egr-1 usually occurs in a transient fashion and required the sequential recruitment in the vicinity of the promoter region of sequence-specific DNAbinding transcription factors followed by chromatin modifiers (Tur et al, 2010). CREB is one of the key players in its regulation.…”

Section: Gra24 Discovery Uncovers a New Regulatory Path Distinct Frommentioning

confidence: 99%

“…The transcription factor is constitutively bound to CRE (cAMP response elements) sites in the Egr-1 promoter. CREB-mediated gene transcription is largely thought to be regulated via its phosphorylation at Ser133 that promotes the recruitment of the co-activator histone acetylase paralogues CBP and p300, which in turn stimulate acetylation of promoter-bound histones and elicit the recruitment of the RNA polymerase II complexes (Tur et al, 2010). A diversity of stimuli induces CREB phosphorylation at Ser133 including those crossing through p38α signalling cascade (Johannessen et al, 2004).…”

Section: Gra24 Discovery Uncovers a New Regulatory Path Distinct Frommentioning

confidence: 99%

Toxoplasmaexports dense granule proteins beyond the vacuole to the host cell nucleus and rewires the host genome expression

2014

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SummaryToxoplasma gondii is the most widespread apicomplexan parasite and occupies a large spectrum of niches by infecting virtually any warmblooded animals. As an obligate intracellular parasite, Toxoplasma has evolved a repertoire of strategies to fine-tune the cellular environment in an optimal way to promote growth and persistence in host tissues hence increasing the chance to be transmitted to new hosts. Short and long-term intracellular survival is associated with Toxoplasma ability to both evade the host deleterious immune defences and to stimulate a beneficial immune balance by governing host cell gene expression. It is only recently that parasite proteins responsible for driving these transcriptional changes have been identified. While proteins contained in the apical secretory Rhoptry organelle have already been identified as bona fide secreted effectors that divert host signalling pathways, recent findings revealed that dense granule proteins should be added to the growing list of effectors as they reach the host cell cytoplasm and nucleus and target various host cell pathways in the course of cell infection. Herein, we emphasize on a novel subfamily of dense granule resident proteins, exemplified with the GRA16 and GRA24 members we recently discovered as both are exported beyond the vacuole-containing parasites and reach the host cell nucleus to reshape the host genome expression.

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Factor binding and chromatin modification in the promoter of murine Egr1 gene upon induction

Cited by 31 publications

References 44 publications

Retroviral Cyclin Controls Cyclin-Dependent Kinase 8-Mediated Transcription Elongation and Reinitiation

Retroviral Cyclin Controls Cyclin-Dependent Kinase 8-Mediated Transcription Elongation and Reinitiation

Chromatin remodeling complex NURF regulates thymocyte maturation

Toxoplasmaexports dense granule proteins beyond the vacuole to the host cell nucleus and rewires the host genome expression

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