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HMGA1 is a novel transcriptional regulator of the FoxO1 gene
Purpose The forkhead transcription factor (FoxO1) is a master transcriptional regulator of fundamental cellular processes ranging from cell proliferation and differentiation to inflammation and metabolism. However, despite its relevance, the mechanism(s) underlying FoxO1 gene regulation are largely...
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Published in: | Endocrine 2018-04, Vol.60 (1), p.56-64 |
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Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Purpose
The forkhead transcription factor (FoxO1) is a master transcriptional regulator of fundamental cellular processes ranging from cell proliferation and differentiation to inflammation and metabolism. However, despite its relevance, the mechanism(s) underlying
FoxO1
gene regulation are largely unknown. We have previously shown that the chromatin factor high-mobility group A1 (HMGA1) plays a key role in the transcriptional regulation of glucose-responsive genes, including some that are involved in FoxO1-mediated glucose metabolism. Here we investigated the impact of HMGA1 on
FoxO1
gene expression.
Methods
FoxO1 protein and gene expression studies were performed by Western blot analysis combined with qRT-PCR of material from human cultured cells and EBV-transformed lymphoblasts, and from primary cultured hepatocytes from wild-type and
Hmga1
–/–
mice. Reporter gene assays and chromatin immunoprecipitation for binding of HMGA1 to the endogenous
FoxoO1
locus were performed in cells overexpressing HMGA1 and in cells pretreated with siRNA targeting HMGA1.
Results
HMGA1 increased FoxO1 mRNA and protein expression in vitro, in cultured HepG2 and HEK-293 cells by binding
FoxO1
gene promoter, thereby activating
FoxO1
gene transcription. Forced expression of HMGA1 in primary cultured hepatocytes from
Hmga1
–/–
mice and in EBV-transformed lymphoblasts from subjects with reduced expression of endogenous HMGA1 increased FoxO1 mRNA and protein levels.
Conclusion
These findings may contribute to the understanding of
FoxO1
gene regulation and its role in metabolism. |
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ISSN: | 1355-008X 1559-0100 |
DOI: | 10.1007/s12020-017-1445-8 |