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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
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Submission date Jun 06, 2023
Last update date Feb 23, 2024
Contact name Mitchell Lazar
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
BioProject PRJNA980596

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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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