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Series GSE234233 Query DataSets for GSE234233
Status Public on Feb 22, 2024
Title Nuclear Receptor Corepressors Non-Canonically Drive Glucocorticoid Receptor-Dependent Activation of Hepatic Gluconeogenesis [ATAC-Seq]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Nuclear receptor corepressors (NCORs) function in multiprotein complexes containing histone deacetylase 3 (HDAC3). In the liver, loss of HDAC3 causes a marked hepatosteatosis largely due to derepression of genes involved in lipid metabolism. Here we show that adult loss of both NCOR1 and 2 (dKO) in hepatocytes phenocopies the hepatomegalic fatty liver phenotype. In addition, dKO livers exhibited a dramatic reduction in glycogen storage and gluconeogenic gene expression that was not observed with hepatic KO of individual NCORs nor HDAC3, resulting in profound fasting hypoglycemia. This surprising HDAC3-independent activation function of NCOR1/2 was due to an unexpected loss of chromatin accessibility upon deletion of NCORs that prevented glucocorticoid receptor binding and stimulatory effect on gluconeogenic genes. These studies reveal an unanticipated, non-canonical activation function of NCORs that is required for metabolic health.
 
Overall design Analysis of chromatin accessibility in HNF4a+ hepatocytes isolated from control and NCOR1/2 dKO livers.
 
Contributor(s) Hauck AK, Lazar MA, Mehmood R
Citation(s) 38622413
Submission date Jun 06, 2023
Last update date Nov 06, 2024
Contact name Mitchell Lazar
E-mail(s) lazar@pennmedicine.upenn.edu
Organization name University of Pennsylvania
Department Perelman School of Medicine
Lab Lazar lab
Street address 3400 Civic Center Blvd
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (6)
GSM7457744 Ncor1/2_ATAC_Cont1
GSM7457745 Ncor1/2_ATAC_Cont2
GSM7457746 Ncor1/2_ATAC_Cont3
This SubSeries is part of SuperSeries:
GSE234234 Nuclear Receptor Corepressors Non-Canonically Drive Glucocorticoid Receptor-Dependent Activation of Hepatic Gluconeogenesis
Relations
BioProject PRJNA980596

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE234233_RAW.tar 3.6 Gb (http)(custom) TAR (of BIGWIG, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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