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Transcription factor GATA4 drives RNA polymerase III-directed transcription and transformed cell proliferation through a filamin A/GATA4/SP1 pathway
RNA polymerase III (pol III) products play fundamental roles in a variety of cellular processes, including protein synthesis and cancer cell proliferation. In addition, dysregulation of pol III-directed transcription closely correlates with tumorigenesis. It is therefore of interest to identify nove...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8857480/ https://www.ncbi.nlm.nih.gov/pubmed/35038452 http://dx.doi.org/10.1016/j.jbc.2022.101581 |
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author | Zhang, Cheng Zhao, Houliang Song, Xiaoye Wang, Juan Zhao, Shasha Deng, Huan He, Liu Zhou, Xiangyu Yin, Xiaomei Zhang, Kewei Zhang, Yue Wu, Zhongyu Chen, Qiyue Du, Jiannan Yu, Deen Zhang, Shihua Deng, Wensheng |
author_facet | Zhang, Cheng Zhao, Houliang Song, Xiaoye Wang, Juan Zhao, Shasha Deng, Huan He, Liu Zhou, Xiangyu Yin, Xiaomei Zhang, Kewei Zhang, Yue Wu, Zhongyu Chen, Qiyue Du, Jiannan Yu, Deen Zhang, Shihua Deng, Wensheng |
author_sort | Zhang, Cheng |
collection | PubMed |
description | RNA polymerase III (pol III) products play fundamental roles in a variety of cellular processes, including protein synthesis and cancer cell proliferation. In addition, dysregulation of pol III-directed transcription closely correlates with tumorigenesis. It is therefore of interest to identify novel pathways or factors governing pol III-directed transcription. Here, we show that transcription factor (TF) GATA binding protein 4 (GATA4) expression in SaOS2 cells was stimulated by the silencing of filamin A (FLNA), a repressor of pol III-directed transcription, suggesting that GATA4 is potentially associated with the regulation of pol III-directed transcription. Indeed, we show that GATA4 expression positively correlates with pol III-mediated transcription and tumor cell proliferation. Mechanistically, we found that GATA4 depletion inhibits the occupancies of the pol III transcription machinery factors at the loci of pol III target genes by reducing expression of both TFIIIB subunit TFIIB-related factor 1 and TFIIIC subunit general transcription factor 3C subunit 2 (GTF3C2). GATA4 has been shown to activate specificity factor 1 (Sp1) gene transcription by binding to the Sp1 gene promoter, and Sp1 has been confirmed to activate pol III gene transcription by directly binding to both Brf1 and Gtf3c2 gene promoters. Thus, the findings from this study suggest that GATA4 links FLNA and Sp1 signaling to form an FLNA/GATA4/Sp1 axis to modulate pol III-directed transcription and transformed cell proliferation. Taken together, these results provide novel insights into the regulatory mechanism of pol III-directed transcription. |
format | Online Article Text |
id | pubmed-8857480 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-88574802022-02-25 Transcription factor GATA4 drives RNA polymerase III-directed transcription and transformed cell proliferation through a filamin A/GATA4/SP1 pathway Zhang, Cheng Zhao, Houliang Song, Xiaoye Wang, Juan Zhao, Shasha Deng, Huan He, Liu Zhou, Xiangyu Yin, Xiaomei Zhang, Kewei Zhang, Yue Wu, Zhongyu Chen, Qiyue Du, Jiannan Yu, Deen Zhang, Shihua Deng, Wensheng J Biol Chem Research Article RNA polymerase III (pol III) products play fundamental roles in a variety of cellular processes, including protein synthesis and cancer cell proliferation. In addition, dysregulation of pol III-directed transcription closely correlates with tumorigenesis. It is therefore of interest to identify novel pathways or factors governing pol III-directed transcription. Here, we show that transcription factor (TF) GATA binding protein 4 (GATA4) expression in SaOS2 cells was stimulated by the silencing of filamin A (FLNA), a repressor of pol III-directed transcription, suggesting that GATA4 is potentially associated with the regulation of pol III-directed transcription. Indeed, we show that GATA4 expression positively correlates with pol III-mediated transcription and tumor cell proliferation. Mechanistically, we found that GATA4 depletion inhibits the occupancies of the pol III transcription machinery factors at the loci of pol III target genes by reducing expression of both TFIIIB subunit TFIIB-related factor 1 and TFIIIC subunit general transcription factor 3C subunit 2 (GTF3C2). GATA4 has been shown to activate specificity factor 1 (Sp1) gene transcription by binding to the Sp1 gene promoter, and Sp1 has been confirmed to activate pol III gene transcription by directly binding to both Brf1 and Gtf3c2 gene promoters. Thus, the findings from this study suggest that GATA4 links FLNA and Sp1 signaling to form an FLNA/GATA4/Sp1 axis to modulate pol III-directed transcription and transformed cell proliferation. Taken together, these results provide novel insights into the regulatory mechanism of pol III-directed transcription. American Society for Biochemistry and Molecular Biology 2022-01-14 /pmc/articles/PMC8857480/ /pubmed/35038452 http://dx.doi.org/10.1016/j.jbc.2022.101581 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Zhang, Cheng Zhao, Houliang Song, Xiaoye Wang, Juan Zhao, Shasha Deng, Huan He, Liu Zhou, Xiangyu Yin, Xiaomei Zhang, Kewei Zhang, Yue Wu, Zhongyu Chen, Qiyue Du, Jiannan Yu, Deen Zhang, Shihua Deng, Wensheng Transcription factor GATA4 drives RNA polymerase III-directed transcription and transformed cell proliferation through a filamin A/GATA4/SP1 pathway |
title | Transcription factor GATA4 drives RNA polymerase III-directed transcription and transformed cell proliferation through a filamin A/GATA4/SP1 pathway |
title_full | Transcription factor GATA4 drives RNA polymerase III-directed transcription and transformed cell proliferation through a filamin A/GATA4/SP1 pathway |
title_fullStr | Transcription factor GATA4 drives RNA polymerase III-directed transcription and transformed cell proliferation through a filamin A/GATA4/SP1 pathway |
title_full_unstemmed | Transcription factor GATA4 drives RNA polymerase III-directed transcription and transformed cell proliferation through a filamin A/GATA4/SP1 pathway |
title_short | Transcription factor GATA4 drives RNA polymerase III-directed transcription and transformed cell proliferation through a filamin A/GATA4/SP1 pathway |
title_sort | transcription factor gata4 drives rna polymerase iii-directed transcription and transformed cell proliferation through a filamin a/gata4/sp1 pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8857480/ https://www.ncbi.nlm.nih.gov/pubmed/35038452 http://dx.doi.org/10.1016/j.jbc.2022.101581 |
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