TRPM3-Induced Gene Transcription Is under Epigenetic Control
Transient receptor potential M3 (TRPM3) cation channels regulate numerous biological functions, including gene transcription. Stimulation of TRPM3 channels with pregnenolone sulfate activates stimulus-responsive transcription factors, which bind to short cognate sequences in the promoters of their t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/7/846 |
| _version_ | 1827604639014453248 |
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| author | Gerald Thiel Oliver G. Rössler |
| author_facet | Gerald Thiel Oliver G. Rössler |
| author_sort | Gerald Thiel |
| collection | DOAJ |
| description | Transient receptor potential M3 (TRPM3) cation channels regulate numerous biological functions, including gene transcription. Stimulation of TRPM3 channels with pregnenolone sulfate activates stimulus-responsive transcription factors, which bind to short cognate sequences in the promoters of their target genes. In addition, coregulator proteins are involved that convert the chromatin into a configuration that is permissive for gene transcription. In this study, we determined whether TRPM3-induced gene transcription requires coactivators that change the acetylation pattern of histones. We used compound A485, a specific inhibitor of the histone acetyltransferases CBP and p300. In addition, the role of bromodomain proteins that bind to acetylated lysine residues of histones was analyzed. We used JQ1, an inhibitor of bromodomain and extra terminal domain (BET) family proteins. The results show that both compounds attenuated the activation of AP-1 and CREB-regulated gene transcription following stimulation of TRPM3 channels. Inhibition of CBP/p300 and BET proteins additionally reduced the transcriptional activation potential of the transcription factors c-Fos and Elk-1. Transcriptional upregulation of the interleukin-8 gene was attenuated by A485 and JQ1, indicating that proinflammatory cytokine expression is controlled by CBP/p300 and bromodomain proteins. We conclude that TRPM3-induced signaling involves transcriptional coactivators and acetyl-lysine-bound bromodomain proteins for activating gene transcription. |
| first_indexed | 2024-03-09T06:03:57Z |
| format | Article |
| id | doaj.art-11b73d7125f44024a05cff7f6ff6765b |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T06:03:57Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-11b73d7125f44024a05cff7f6ff6765b2023-12-03T12:05:37ZengMDPI AGPharmaceuticals1424-82472022-07-0115784610.3390/ph15070846TRPM3-Induced Gene Transcription Is under Epigenetic ControlGerald Thiel0Oliver G. Rössler1Department of Medical Biochemistry and Molecular Biology, Saarland University, Building 44, 66421 Homburg, GermanyDepartment of Medical Biochemistry and Molecular Biology, Saarland University, Building 44, 66421 Homburg, GermanyTransient receptor potential M3 (TRPM3) cation channels regulate numerous biological functions, including gene transcription. Stimulation of TRPM3 channels with pregnenolone sulfate activates stimulus-responsive transcription factors, which bind to short cognate sequences in the promoters of their target genes. In addition, coregulator proteins are involved that convert the chromatin into a configuration that is permissive for gene transcription. In this study, we determined whether TRPM3-induced gene transcription requires coactivators that change the acetylation pattern of histones. We used compound A485, a specific inhibitor of the histone acetyltransferases CBP and p300. In addition, the role of bromodomain proteins that bind to acetylated lysine residues of histones was analyzed. We used JQ1, an inhibitor of bromodomain and extra terminal domain (BET) family proteins. The results show that both compounds attenuated the activation of AP-1 and CREB-regulated gene transcription following stimulation of TRPM3 channels. Inhibition of CBP/p300 and BET proteins additionally reduced the transcriptional activation potential of the transcription factors c-Fos and Elk-1. Transcriptional upregulation of the interleukin-8 gene was attenuated by A485 and JQ1, indicating that proinflammatory cytokine expression is controlled by CBP/p300 and bromodomain proteins. We conclude that TRPM3-induced signaling involves transcriptional coactivators and acetyl-lysine-bound bromodomain proteins for activating gene transcription.https://www.mdpi.com/1424-8247/15/7/846AP-1A485BET proteinsbromodomainElk-1interleukin-8 |
| spellingShingle | Gerald Thiel Oliver G. Rössler TRPM3-Induced Gene Transcription Is under Epigenetic Control Pharmaceuticals AP-1 A485 BET proteins bromodomain Elk-1 interleukin-8 |
| title | TRPM3-Induced Gene Transcription Is under Epigenetic Control |
| title_full | TRPM3-Induced Gene Transcription Is under Epigenetic Control |
| title_fullStr | TRPM3-Induced Gene Transcription Is under Epigenetic Control |
| title_full_unstemmed | TRPM3-Induced Gene Transcription Is under Epigenetic Control |
| title_short | TRPM3-Induced Gene Transcription Is under Epigenetic Control |
| title_sort | trpm3 induced gene transcription is under epigenetic control |
| topic | AP-1 A485 BET proteins bromodomain Elk-1 interleukin-8 |
| url | https://www.mdpi.com/1424-8247/15/7/846 |
| work_keys_str_mv | AT geraldthiel trpm3inducedgenetranscriptionisunderepigeneticcontrol AT olivergrossler trpm3inducedgenetranscriptionisunderepigeneticcontrol |