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Titel: TRPM3-Induced Gene Transcription Is under Epigenetic Control
VerfasserIn: Thiel, Gerald
Rössler, Oliver G.
Sprache: Englisch
Titel: Pharmaceuticals
Bandnummer: 15
Heft: 7
Verlag/Plattform: MDPI
Erscheinungsjahr: 2022
Freie Schlagwörter: AP-1
A485
BET proteins
bromodomain
Elk-1
interleukin-8
JQ1
CREB
TRPM3
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: 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.
DOI der Erstveröffentlichung: 10.3390/ph15070846
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-369016
hdl:20.500.11880/33594
http://dx.doi.org/10.22028/D291-36901
ISSN: 1424-8247
Datum des Eintrags: 8-Aug-2022
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Medizinische Biochemie und Molekularbiologie
Professur: M - Prof. Dr. Gerald Thiel
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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