Screening of transcription factors with transcriptional initiation activity

Zhang, Lang; Yu, Haoyue; Wang, Pan; Ding, Qingyang; Zhao, Wei

doi:10.1016/j.gene.2013.07.054

Cited by 6 publications

(7 citation statements)

References 34 publications

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“…While CpG island promoters represent the majority of mammalian promoters [47,48], they generally lack core promoter elements, and have dispersed transcription initiation sites as compared to TATA box-containing promoters, which usually have focused transcription initiation site [47][48][49][50]. It has been suggested that, in CpG island promoters, transcription factors can interact with the basal transcription machinery to activate transcription without core promoter elements defining the precise binding of the transcription apparatus, leading to dispersed transcription initiation sites [50,51]. Zhang et al [50] recently reported that, while transcription factors, such as SP1, have little transcriptional initiation capacity, members of the E-twenty six (ETS) family, nuclear respiratory factor 1 (NRF1), and the basic helix-loop-helix/ leucine zipper (bHLH/ZIP) family of proteins showed a strong transcriptional initiation activity.…”

Section: Pannexin1 Promoter In the Epididymismentioning

confidence: 99%

“…It has been suggested that, in CpG island promoters, transcription factors can interact with the basal transcription machinery to activate transcription without core promoter elements defining the precise binding of the transcription apparatus, leading to dispersed transcription initiation sites [50,51]. Zhang et al [50] recently reported that, while transcription factors, such as SP1, have little transcriptional initiation capacity, members of the E-twenty six (ETS) family, nuclear respiratory factor 1 (NRF1), and the basic helix-loop-helix/ leucine zipper (bHLH/ZIP) family of proteins showed a strong transcriptional initiation activity. Transcription of the reporter gene initiated by these transcription factors was also initiated at multiple sites [50].…”

Section: Pannexin1 Promoter In the Epididymismentioning

confidence: 99%

“…Zhang et al [50] recently reported that, while transcription factors, such as SP1, have little transcriptional initiation capacity, members of the E-twenty six (ETS) family, nuclear respiratory factor 1 (NRF1), and the basic helix-loop-helix/ leucine zipper (bHLH/ZIP) family of proteins showed a strong transcriptional initiation activity. Transcription of the reporter gene initiated by these transcription factors was also initiated at multiple sites [50]. The present observations suggest that the Panx1 gene is likely to be initiated by transcription factors, which would explain the multiple start sites observed with RACE experiments.…”

Section: Pannexin1 Promoter In the Epididymismentioning

confidence: 99%

“…The present observations suggest that the Panx1 gene is likely to be initiated by transcription factors, which would explain the multiple start sites observed with RACE experiments. Transcription factors, such as ETV4, a member of the ETS family, and CREB, a member of the basic leucine zipper family of transcription factors, possess the ability to initiate transcription [50]. These transcription factors could act together with other regulators of transcription in binding to GC-rich regions, such as SP1, since multiple putative binding sites for this protein were detected in the Panx1 promoter, to regulate the Panx1 transcription.…”

Section: Pannexin1 Promoter In the Epididymismentioning

confidence: 99%

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Regulation of the Pannexin-1 Promoter in the Rat Epididymis1

Dufresne¹,

Cyr²

2014

Biology of Reproduction

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Pannexins (PANXs) are channel-forming proteins implicated in cellular communication through the secretion of biomolecules, such as ATP and glutamate. PANX1 and PANX3 are expressed in the male rat reproductive tract and their levels are regulated by androgens in the epididymis. There is currently no information on the regulation of the Panx1 promoter. The objective of the present study was to characterize the Panx1 promoter in order to understand its regulation in the epididymis. RNA ligase-mediated rapid amplification of cDNA ends identified three transcriptional start sites, at positions -443, -429, and -393. In silico analysis revealed that transcription was initiated downstream of binding sites for CREB and ETV4 transcription factors, in a CpG island context. To determine the importance of this region in gene transactivation, a 2-kb fragment of the promoter was cloned into a vector containing a luciferase reporter gene. Deletion constructs indicated that the highest transactivation levels were achieved with shorter constructs (-973 to -346 and -550 to -346). Electrophoretic mobility shift assay and supershifts indicated that both transcription factors were able to bind to the promoter region. Chromatin immunoprecipitation using rat caput epididymis cells confirmed the binding of ETV4 and CREB on the Panx1 promoter. Site mutation of either the ETV4 or CREB binding site decreased the transactivation of the reporter gene. Previous studies indicated that orchidectomy increased epididymal PANX1 levels. Likewise, we observed an increase in both ETV4 and CREB in orchidectomized rats. These results indicate that ETV4 and cAMP response elements play a role in the transcriptional regulation of Panx1 in the epididymis.

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Section: Pannexin1 Promoter In the Epididymismentioning

confidence: 99%

Section: Pannexin1 Promoter In the Epididymismentioning

confidence: 99%

Section: Pannexin1 Promoter In the Epididymismentioning

confidence: 99%

Section: Pannexin1 Promoter In the Epididymismentioning

confidence: 99%

See 2 more Smart Citations

Regulation of the Pannexin-1 Promoter in the Rat Epididymis1

Dufresne¹,

Cyr²

2014

Biology of Reproduction

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“…From our analysis, GABPA demonstrated the highest possibility for regulating the four gene candidates followed by ELK1 and SP1. GABPA, SP1 and ELK1 have common cis-regulatory elements and probably form a complex as a result of E7 activation [23]. A previous study has mentioned that GABPA likely interacts with SP1 and plays a part in regulating broad biological processes such as; embryonic development, cell differentiation, mitochondrial biogenesis and the cell cycle [24].…”

Section: Discussionmentioning

confidence: 99%

Host proteome linked to HPV E7-mediated specific gene hypermethylation in cancer pathways

Rangsee

Yanatatsaneejit

Pisitkun

et al. 2020

Infect Agents Cancer

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Background: Human papillomavirus (HPV) infection causes around 90% of cervical cancer cases, and cervical cancer is a leading cause of female mortality worldwide. HPV-derived oncoprotein E7 participates in cervical carcinogenesis by inducing aberrant host DNA methylation. However, the targeting specificity of E7 methylation of host genes is not fully understood but is important in the down-regulation of crucial proteins of the hallmark cancer pathways. In this study, we aim to link E7-driven aberrations in the host proteome to corresponding gene promoter hypermethylation events in the hope of providing novel therapeutic targets and biomarkers to indicate the progression of cervical cancer. Methods: HEK293 cells were transfected with pcDNA3.1-E7 plasmid and empty vector and subjected to mass spectrometry-based proteomic analysis. Down-regulated proteins (where relative abundance was determined significant by paired T-test) relevant to cancer pathways were selected as gene candidates for mRNA transcript abundance measurement by qPCR and expression compared with that in SiHa cells (HPV type 16 positive). Methylation Specific PCR was used to determine promoter hypermethylation in genes downregulated in both SiHa and transfected HEK293 cell lines. The FunRich and STRING databases were used for identification of potential regulatory transcription factors and the proteins interacting with transcription factor gene candidates, respectively. Results: Approximately 400 proteins totally were identified in proteomics analysis. The transcripts of six genes involved in the host immune response and cell proliferation (PTMS, C1QBP, BCAP31, CDKN2A, ZMYM6 and HIST1H1D) were down-regulated, corresponding to proteomic results. Methylation assays showed four gene promoters (PTMS, C1QBP, BCAP31 and CDKN2A) were hypermethylated with 61, 55.5, 70 and 78% increased methylation, respectively. Those four genes can be regulated by the GA-binding protein alpha chain, specificity protein 1 and ETS-like protein-1 transcription factors, as identified from FunRich database predictions. Conclusions: HPV E7 altered the HEK293 proteome, particularly with respect to proteins involved in cell proliferation and host immunity. Down-regulation of these proteins appears to be partly mediated via host DNA methylation. E7 possibly complexes with the transcription factors of its targeting genes and DNMT1, allowing methylation of specific target gene promoters.

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