Academic Journal
TFII-I-mediated polymerase pausing antagonizes GLI2 induction by TGFβ
| العنوان: | TFII-I-mediated polymerase pausing antagonizes GLI2 induction by TGFβ |
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| المؤلفون: | McCleary-Wheeler, Angela L, Paradise, Brooke D, Almada, Luciana L, Carlson, Annika J, Marks, David L, Vrabel, Anne, Vera, Renzo E, Sigafoos, Ashley N, Olson, Rachel L, Fernandez-Zapico, Martin E |
| المساهمون: | National Institutes of Health, National Cancer Institute, Mayo Clinic, Mayo Clinic Cancer for Cell Signaling in Gastroenterology |
| المصدر: | Nucleic Acids Research ; ISSN 0305-1048 1362-4962 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2020 |
| الوصف: | The modulation of GLI2, an oncogenic transcription factor commonly upregulated in cancer, is in many cases not due to genetic defects, suggesting dysregulation through alternative mechanisms. The identity of these molecular events remains for the most part unknown. Here, we identified TFII-I as a novel repressor of GLI2 expression. Mapping experiments suggest that the INR region of the GLI2 promoter is necessary for GLI2 repression. ChIP studies showed that TFII-I binds to this INR. TFII-I knockdown decreased the binding of NELF-A, a component of the promoter–proximal pausing complex at this site, and enriched phosphorylated RNAPII serine 2 in the GLI2 gene body. Immunoprecipitation studies demonstrate TFII-I interaction with SPT5, another pausing complex component. TFII-I overexpression antagonized GLI2 induction by TGFβ, a known activator of GLI2 in cancer cells. TGFβ reduced endogenous TFII-I binding to the INR and increased RNAPII SerP2 in the gene body. We demonstrate that this regulatory mechanism is not exclusive of GLI2. TGFβ-induced genes CCR7, TGFβ1 and EGR3 showed similar decreased TFII-I and NELF-A INR binding and increased RNAPII SerP2 in the gene body post-TGFβ treatment. Together these results identify TFII-I as a novel repressor of a subset of TGFβ-responsive genes through the regulation of RNAPII pausing. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/nar/gkaa476 |
| DOI: | 10.1093/nar/gkaa476/33394218/gkaa476.pdf |
| الاتاحة: | https://doi.org/10.1093/nar/gkaa476 http://academic.oup.com/nar/advance-article-pdf/doi/10.1093/nar/gkaa476/33394218/gkaa476.pdf |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.4E8C5CDD |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/nar/gkaa476 |
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