Egr-1 regulates the transcription of the BRCA1 gene by etoposide

Shin, Soon Young; Kim, Chang Gun; Lee, Young Han

doi:10.5483/bmbrep.2013.46.2.202

Cited by 17 publications

(19 citation statements)

References 21 publications

(21 reference statements)

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“…Indeed, regions targeted with sgRNA-2, sgRNA-3, and sgRNA-4 are enriched with multiple transcription factors, including Sp1 and Egr-1, as predicted using TransFac. Sp1 and Egr-1 are activators of BRCA1 [41, 42] and their binding to DNA is known to be impaired by DNA methylation [43, 44]. Hence the reversal of methylation, i.e., demethylation, can be logically considered to facilitate transcription factor binding to DNA and subsequent initiation of transcription.…”

Section: Resultsmentioning

confidence: 99%

CRISPR-dCas9 mediated TET1 targeting for selective DNA demethylation at BRCA1 promoter

et al. 2016

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DNA hypermethylation at the promoter of tumour-suppressor genes is tightly correlated with their transcriptional repression and recognized as the hallmark of majority of cancers. Epigenetic silencing of tumour suppressor genes impairs their cellular functions and activates a cascade of events driving cell transformation and cancer progression. Here, we examine site-specific and spatiotemporal alteration in DNA methylation at a target region in BRCA1 gene promoter, a model tumour suppressor gene. We have developed a programmable CRISPR-Cas9 based demethylase tool containing the deactivated Cas9 (dCas9) fused to the catalytic domain (CD) of Ten-Eleven Translocation (TET) dioxygenase1 (TET1CD). The fusion protein selectively demethylates targeted regions within BRCA1 promoter as directed by the designed single-guide RNAs (sgRNA), leading to the transcriptional up-regulation of the gene. We also noticed the increment in 5-hydroxymethylation content (5-hmC) at the target DNA site undergoing the most profound demethylation. It confirms the catalytic activity of TET1 in TET1-dCas9 fusion proteins-mediated demethylation at these target sequences. The modular design of the fusion constructs presented here allows for the selective substitution of other chromatin or DNA modifying enzymes and for loci-specific targeting to uncover epigenetic regulatory pathways at gene promoters and other selected genomic regions.

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Section: Resultsmentioning

confidence: 99%

CRISPR-dCas9 mediated TET1 targeting for selective DNA demethylation at BRCA1 promoter

et al. 2016

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“…EGR-1 transcription factor, which is expressed in the nervous system, suits as a potential candidate since it has been shown to be upregulated -mRNA and protein-in response to DNA damage, and to behave as a prosurvival factor following ionizing and UV radiation. [38][39][40][41][42] Considering these evidence, we suggest EGR-1 as an upstream regulator of E2F1 and E2F2 induction upon DNA damage. Although EGR-1 has many potential binding sites in both E2F1 and E2F2 promoters, we speculate that in E2F2 promoter in neuronal cells it might associate with coactivators necessary to promote its transcription upon genotoxic stress.…”

Section: Discussionmentioning

confidence: 99%

E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells

et al. 2015

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Abbreviations: ODN, oligodeoxynucleotide; NCS, neocarzinostatin; ASCAT, CAT antisense; ASE2F1, E2F1 antisense; ASE2F2, E2F2 antisense; wt E2F DO, wild-type E2F decoy oligodeoxynucleotide; mut E2F DO, mutant E2F decoy oligodeoxynucleotide.E2F transcription factors regulate a wide range of biological processes, including the cellular response to DNA damage. In the present study, we examined whether E2F family members are transcriptionally induced following treatment with several genotoxic agents, and have a role on the cell DNA damage response. We show a novel mechanism, conserved among diverse species, in which E2F1 and E2F2, the latter specifically in neuronal cells, are transcriptionally induced after DNA damage. This upregulation leads to increased E2F1 and E2F2 protein levels as a consequence of de novo protein synthesis. Ectopic expression of these E2Fs in neuronal cells reduces the level of DNA damage following genotoxic treatment, while ablation of E2F1 and E2F2 leads to the accumulation of DNA lesions and increased apoptotic response. Cell viability and DNA repair capability in response to DNA damage induction are also reduced by the E2F1 and E2F2 deficiencies. Finally, E2F1 and E2F2 accumulate at sites of oxidative and UV-induced DNA damage, and interact with gH2AX DNA repair factor. As previously reported for E2F1, E2F2 promotes Rad51 foci formation, interacts with GCN5 acetyltransferase and induces histone acetylation following genotoxic insult. The results presented here unveil a new mechanism involving E2F1 and E2F2 in the maintenance of genomic stability in response to DNA damage in neuronal cells.

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“…The nuclear extracts of cells were prepared and analyzed for NF-κB binding activity by EMSA, as described previously (22).…”

Section: Electrophoretic Mobility Shift Assay (Emsa)mentioning

confidence: 99%

Salicortin suppresses lipopolysaccharide-stimulated inflammatory responses via blockade of NF-κB and JNK activation in RAW 264.7 macrophages

Kwon¹,

Bae²,

Ju³

et al. 2014

BMB Reports

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We isolated the phenolic glucoside salicortin from a Populus euramericana bark extract, and examined its ability to suppress inflammatory responses as well as the molecular mechanisms underlying these abilities, using lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Salicortin inhibited iNOS expression and the subsequent production of NO in a dose-dependent manner in the LPS-stimulated RAW 264.7 cells. Salicortin significantly suppressed LPS-induced signal cascades of NF-κB activation, such as IKK activation, IκBα phosphorylation and p65 phosphorylation in RAW 264.7 cells. In addition, salicortin inhibited the LPS-induced activation of JNK, but not ERK or p38 MAPK. Furthermore, salicortin significantly inhibited production of pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6 in the LPS-stimulated RAW 264.7 cells. These findings suggest that salicortin may show its anti-inflammatory activity by suppressing the LPS-induced expression of pro-inflammatory mediators through inhibition of NF-κB and JNK MAPK signaling cascades in macrophages. [BMB Reports 2014; 47(6): 318-323]

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Egr-1 regulates the transcription of the BRCA1 gene by etoposide

Cited by 17 publications

References 21 publications

CRISPR-dCas9 mediated TET1 targeting for selective DNA demethylation at BRCA1 promoter

CRISPR-dCas9 mediated TET1 targeting for selective DNA demethylation at BRCA1 promoter

E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells

Salicortin suppresses lipopolysaccharide-stimulated inflammatory responses via blockade of NF-κB and JNK activation in RAW 264.7 macrophages

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