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SETDB2 Links Glucocorticoid to Lipid Metabolism through Insig2a Regulation
- Publication Year :
- 2016
-
Abstract
- Transcriptional and chromatin regulations mediate the liver response to nutrient availability. The role of chromatin factors involved in hormonal regulation in response to fasting is not fully understood. We have identified SETDB2, a glucocorticoid-induced putative epigenetic modifier, as a positive regulator of GR-mediated gene activation in liver. Insig2a increases during fasting to limit lipid synthesis, but the mechanism of induction is unknown. We show Insig2a induction is GR-SETDB2 dependent. SETDB2 facilitates GR chromatin enrichment and is key to glucocorticoid-dependent enhancer-promoter interactions. INSIG2 is a negative regulator of SREBP, and acute glucocorticoid treatment decreased active SREBP during refeeding or in livers of Ob/Ob mice, both systems of elevated SREBP-1c-driven lipogenesis. Knockdown of SETDB2 or INSIG2 reversed the inhibition of SREBP processing. Overall, these studies identify a GR-SETDB2 regulatory axis of hepatic transcriptional reprogramming and identify SETDB2 as a potential target for metabolic disorders with aberrant glucocorticoid actions.
- Subjects :
- 0301 basic medicine
Male
Transcription, Genetic
Physiology
Regulator
Mice, Obese
Biológiai tudományok
Dexamethasone
Histones
0302 clinical medicine
Glucocorticoid receptor
Természettudományok
Promoter Regions, Genetic
Regulation of gene expression
Chromatin
Enhancer Elements, Genetic
Liver
Gene Knockdown Techniques
Lipogenesis
Sterol Regulatory Element Binding Protein 1
Glucocorticoid
medicine.drug
Protein Binding
medicine.medical_specialty
Biology
Methylation
Article
03 medical and health sciences
Receptors, Glucocorticoid
Internal medicine
medicine
Animals
RNA, Messenger
Molecular Biology
Glucocorticoids
Lysine
Membrane Proteins
Lipid metabolism
Cell Biology
Feeding Behavior
Histone-Lysine N-Methyltransferase
Lipid Metabolism
Sterol regulatory element-binding protein
Mice, Inbred C57BL
030104 developmental biology
Endocrinology
Gene Expression Regulation
Genetic Loci
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....fba4e877075e9af081e81974ababca29