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Specificity protein 1 transcription factor regulates human ARTS promoter activity through multiple binding sites.

Xu F, Sun W, Li P, Chen J, Zhu D, Sun X, Wang J, Feng J, Song K, Duan Y - PLoS ONE (2015)

Bottom Line: Apoptosis-related protein in the TGF-β signaling pathway (ARTS) is an unusual mitochondrial Septin-like protein which functions as a tumor suppressor.ChIP analysis showed that Sp1 protein could bind to two of these sites (-735/-718 and -173/-157) and mutation of each Sp1 binding site led to a significant decrease in ARTS promoter activity.This would provide basis for further study on the function of ARTS on cell apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China; Clinical Laboratory, The Sixth People's Hospital of Nantong, Nantong 226001, Jiangsu, People's Republic of China.

ABSTRACT
Apoptosis-related protein in the TGF-β signaling pathway (ARTS) is an unusual mitochondrial Septin-like protein which functions as a tumor suppressor. There are various splice variants derived from the human Septin4 gene, one of which is ARTS, also known as Septin4_i2. Unlike other Septin4 members, ARTS can induce apoptosis in many cells, however, the underlying molecular mechanism for the transcriptional regulation of ARTS has yet to be deciphered. In this study, we attempted to analyze the promoter region of ARTS in cultured HEK-293T and LX-2 cells with the purpose of elucidating the underlying transcriptional mechanisms driving ARTS expression. We effectively demonstrated that the -824 to -5 bp region of the ARTS promoter was essential for ARTS transcription and identified four putative specificity protein 1 (Sp1) binding sites within this core promoter region. ChIP analysis showed that Sp1 protein could bind to two of these sites (-735/-718 and -173/-157) and mutation of each Sp1 binding site led to a significant decrease in ARTS promoter activity. In conclusion, all the results indicated that the Sp1 transcription factor could contribute to ARTS gene transcription. The underlying molecular events of the specific promoter of ARTS could also be used to explain why ARTS is selectively silenced during some human diseases. This would provide basis for further study on the function of ARTS on cell apoptosis.

No MeSH data available.


Related in: MedlinePlus

Putative transcription factor binding sites in ARTS promoter.The binding sites in the region from -824 to -5 bp of the promoter were screened using TFSEARCH and MatInspector. Boxed sequences indicate the predicted sites.
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pone.0120072.g002: Putative transcription factor binding sites in ARTS promoter.The binding sites in the region from -824 to -5 bp of the promoter were screened using TFSEARCH and MatInspector. Boxed sequences indicate the predicted sites.

Mentions: The results above revealed that the region from -824 bp to -5 bp is responsible for the expression of the ARTS gene. We thus sought to identify transcription factors which could be involved in this regulation. By using the MatInspector and TFSEARCH tool, we found numerous putative transcription factor binding sites in the region from -824 bp to -5 bp, including binding sites for Sp1, GATA-1, MZF1 as well as other transcription factors (Fig. 2). It is known that Sp1 plays a critical role in the basal level of transcription in the majority of promoters containing Sp1-binding sites [26,27] and that it is able to activate transcription initiation through recruiting the TATA binding protein-transcription factor IID (TBP-TFIID) complex in TATA-less promoter regions [28]. Hence, we hypothesized that Sp1 binding sites might contribute to the regulation of ARTS expression and we focused our further study on this topic.


Specificity protein 1 transcription factor regulates human ARTS promoter activity through multiple binding sites.

Xu F, Sun W, Li P, Chen J, Zhu D, Sun X, Wang J, Feng J, Song K, Duan Y - PLoS ONE (2015)

Putative transcription factor binding sites in ARTS promoter.The binding sites in the region from -824 to -5 bp of the promoter were screened using TFSEARCH and MatInspector. Boxed sequences indicate the predicted sites.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4366172&req=5

pone.0120072.g002: Putative transcription factor binding sites in ARTS promoter.The binding sites in the region from -824 to -5 bp of the promoter were screened using TFSEARCH and MatInspector. Boxed sequences indicate the predicted sites.
Mentions: The results above revealed that the region from -824 bp to -5 bp is responsible for the expression of the ARTS gene. We thus sought to identify transcription factors which could be involved in this regulation. By using the MatInspector and TFSEARCH tool, we found numerous putative transcription factor binding sites in the region from -824 bp to -5 bp, including binding sites for Sp1, GATA-1, MZF1 as well as other transcription factors (Fig. 2). It is known that Sp1 plays a critical role in the basal level of transcription in the majority of promoters containing Sp1-binding sites [26,27] and that it is able to activate transcription initiation through recruiting the TATA binding protein-transcription factor IID (TBP-TFIID) complex in TATA-less promoter regions [28]. Hence, we hypothesized that Sp1 binding sites might contribute to the regulation of ARTS expression and we focused our further study on this topic.

Bottom Line: Apoptosis-related protein in the TGF-β signaling pathway (ARTS) is an unusual mitochondrial Septin-like protein which functions as a tumor suppressor.ChIP analysis showed that Sp1 protein could bind to two of these sites (-735/-718 and -173/-157) and mutation of each Sp1 binding site led to a significant decrease in ARTS promoter activity.This would provide basis for further study on the function of ARTS on cell apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China; Clinical Laboratory, The Sixth People's Hospital of Nantong, Nantong 226001, Jiangsu, People's Republic of China.

ABSTRACT
Apoptosis-related protein in the TGF-β signaling pathway (ARTS) is an unusual mitochondrial Septin-like protein which functions as a tumor suppressor. There are various splice variants derived from the human Septin4 gene, one of which is ARTS, also known as Septin4_i2. Unlike other Septin4 members, ARTS can induce apoptosis in many cells, however, the underlying molecular mechanism for the transcriptional regulation of ARTS has yet to be deciphered. In this study, we attempted to analyze the promoter region of ARTS in cultured HEK-293T and LX-2 cells with the purpose of elucidating the underlying transcriptional mechanisms driving ARTS expression. We effectively demonstrated that the -824 to -5 bp region of the ARTS promoter was essential for ARTS transcription and identified four putative specificity protein 1 (Sp1) binding sites within this core promoter region. ChIP analysis showed that Sp1 protein could bind to two of these sites (-735/-718 and -173/-157) and mutation of each Sp1 binding site led to a significant decrease in ARTS promoter activity. In conclusion, all the results indicated that the Sp1 transcription factor could contribute to ARTS gene transcription. The underlying molecular events of the specific promoter of ARTS could also be used to explain why ARTS is selectively silenced during some human diseases. This would provide basis for further study on the function of ARTS on cell apoptosis.

No MeSH data available.


Related in: MedlinePlus