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FoxO1 and FoxA1/2 form a complex on DNA and cooperate to open chromatin at insulin-regulated genes.
- Source :
-
Biochemistry and cell biology = Biochimie et biologie cellulaire [Biochem Cell Biol] 2019 Apr; Vol. 97 (2), pp. 118-129. Date of Electronic Publication: 2018 Aug 24. - Publication Year :
- 2019
-
Abstract
- 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.
- Subjects :
- Chromatin genetics
DNA genetics
Forkhead Box Protein O1 genetics
Hep G2 Cells
Hepatocyte Nuclear Factor 3-alpha genetics
Hepatocyte Nuclear Factor 3-beta genetics
Humans
Insulin genetics
Insulin-Like Growth Factor Binding Protein 1 biosynthesis
Insulin-Like Growth Factor Binding Protein 1 genetics
Phosphorylation genetics
RNA Polymerase II genetics
RNA Polymerase II metabolism
Response Elements
Chromatin metabolism
DNA metabolism
Forkhead Box Protein O1 metabolism
Hepatocyte Nuclear Factor 3-alpha metabolism
Hepatocyte Nuclear Factor 3-beta metabolism
Insulin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1208-6002
- Volume :
- 97
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemistry and cell biology = Biochimie et biologie cellulaire
- Publication Type :
- Academic Journal
- Accession number :
- 30142277
- Full Text :
- https://doi.org/10.1139/bcb-2018-0104