FoxO1 and FoxA1/2 form a complex on DNA and cooperate to open chromatin at insulin-regulated genes
| العنوان: | FoxO1 and FoxA1/2 form a complex on DNA and cooperate to open chromatin at insulin-regulated genes |
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| المؤلفون: | Lisa Ann Cirillo, Joshua Nord, Daniel Schill |
| المصدر: | Biochemistry and Cell Biology. 97:118-129 |
| بيانات النشر: | Canadian Science Publishing, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Hepatocyte Nuclear Factor 3-alpha, endocrine system, FOXO1, RNA polymerase II, Biology, Response Elements, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Transcription (biology), Humans, Insulin, Phosphorylation, Molecular Biology, Gene, 030304 developmental biology, 0303 health sciences, Forkhead Box Protein O1, Promoter, DNA, Hep G2 Cells, Cell Biology, Chromatin, Cell biology, Insulin-Like Growth Factor Binding Protein 1, chemistry, Acetylation, Hepatocyte Nuclear Factor 3-beta, biology.protein, RNA Polymerase II, 030217 neurology & neurosurgery |
| الوصف: | We have previously shown that cooperative, interdependent binding by the pioneer factors FoxO1 and FoxA1/2 is required for recruitment of RNA polymerase II and H3K27 acetylation to the promoters of insulin-regulated genes. However, the underlying mechanisms are unknown. In this study, we demonstrate that, in HepG2 cells, FoxO1 and FoxA2 form a complex on DNA that is disrupted by insulin treatment. Insulin-mediated phosphorylation of FoxO1 and FoxA2 does not impair their cooperative binding to mononucleosome particles assembled from the IGFBP1 promoter, indicating that direct disruption of complex formation by phosphorylation is not responsible for the loss of interdependent FoxO1:FoxA1/2 binding following insulin treatment. Since FoxO1 and FoxA1/2 binding is required for the establishment and maintenance of transcriptionally active chromatin at insulin-regulated genes, we hypothesized that cooperative FoxO1 and FoxA1/2 binding dictates the chromatin remodeling events required for the initial activation of these genes. In support of this idea, we demonstrate that FoxO1 and FoxA2 cooperatively open linker histone compacted chromatin templates containing the IGFBP1 promoter. Taken together, these results provide a mechanism for how interdependent FoxO1:FoxA1/2 binding is negatively impacted by insulin and provide a developmental context for cooperative gene activation by these factors. |
| تدمد: | 1208-6002 0829-8211 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e2767ccf469c272925173f8b0ab7e01dTest https://doi.org/10.1139/bcb-2018-0104Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....e2767ccf469c272925173f8b0ab7e01d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 12086002 08298211 |
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