Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Short-term cold exposure induces persistent epigenomic memory in brown fat [ATAC-Seq]

ABSTRACT: Deficiency of the epigenome modulator histone deacetylase 3 (HDAC3) in brown adipose tissue (BAT) impairs the ability of mice to survive in near-freezing temperatures. Here, we report that short-term exposure to mild cold temperature (STEMCT: 15°C for 24 hours) averted lethal hypothermia of mice lacking HDAC3 in BAT (HDAC3 BAT KO) exposed to 4°C. STEMCT restored the induction of the thermogenic coactivator PGC-1a along with UCP1 at 22°C, which is greatly impaired in HDAC3-deficient BAT, and deletion of either UCP1 or PGC-1a prevented the protective effect of STEMCT. Remarkably, the protection of HDAC3 BAT KO mice from cold intolerance following STEMCT lasted for up to 7 days. Transcriptional activator C/EBPb was induced by short-term cold exposure in mouse and human BAT and, uniquely, remained high for 7 days following STEMCT. Furthermore, analysis of C/EBPb activity revealed increased binding following STEMCT at genes, including the enhancers/promotors of UCP1 and PGC-1a. These results reveal the existence of a cold-adaptive epigenomic memory mediated by C/EBPb that is persistent and HDAC3-independent.

ORGANISM(S): Mus musculus

PROVIDER: GSE244382 | GEO | 2024/07/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Short-term cold exposure induces persistent epigenomic memory in brown fat [ChIP-Seq

Project description:Deficiency of the epigenome modulator histone deacetylase 3 (HDAC3) in brown adipose tissue (BAT) impairs the ability of mice to survive in near-freezing temperatures. Here, we report that short-term exposure to mild cold temperature (STEMCT: 15°C for 24 hours) averted lethal hypothermia of mice lacking HDAC3 in BAT (HDAC3 BAT KO) exposed to 4°C. STEMCT restored the induction of the thermogenic coactivator PGC-1a along with UCP1 at 22°C, which is greatly impaired in HDAC3-deficient BAT, and deletion of either UCP1 or PGC-1a prevented the protective effect of STEMCT. Remarkably, the protection of HDAC3 BAT KO mice from cold intolerance following STEMCT lasted for up to 7 days. Transcriptional activator C/EBPb was induced by short-term cold exposure in mouse and human BAT and, uniquely, remained high for 7 days following STEMCT. Furthermore, analysis of C/EBPb activity revealed increased binding following STEMCT at genes, including the enhancers/promotors of UCP1 and PGC-1a. These results reveal the existence of a cold-adaptive epigenomic memory mediated by C/EBPb that is persistent and HDAC3-independent.

2024-07-05 | GSE244383 | GEO

Short-term cold exposure induces persistent epigenomic memory in brown fat [RNA-Seq]

2024-07-05 | GSE244385 | GEO

Short-term cold exposure induces persistent epigenomic memory in brown fat [GRO-Seq]

2024-07-05 | GSE244384 | GEO

Histone Deacetylase 3 Prepares Brown Adipose Tissue For Acute Thermogenic Challenge [RNA-Seq]

Project description:Brown adipose tissue (BAT) is a thermogenic organ that requires Uncoupling Protein 1 (UCP1) to dissipate chemical energy as heat, to defend core body temperature against hypothermia, and counteract obesity and metabolic diseases1. However, the transcriptional mechanism ensuring BAT thermogenic capacity for survival prior to environmental cold is unknown. Here we show histone deacetylase 3 (HDAC3) is a required transcriptional regulator of BAT enhancers to ensure thermogenic aptitude and survival. Mice with genetic ablation of HDAC3 become severely hypothermic and fail to survive acute cold exposure. UCP1 is nearly absent in BAT lacking HDAC3 and there is marked down-regulation of mitochondrial oxidative phosphorylation (OXPHOS) genes. Remarkably, although HDAC3 canonically functions as a transcriptional corepressor2, HDAC3 functions as a coactivator of the estrogen-related receptor _ (ERR_) in BAT, and loss of HDAC3 leads to robust global down-regulation of ERR±-driven enhancers. HDAC3 coactivation of ERR_ is mediated through deacetylation of PGC-1_ and is required for basal transcription of Ucp1, OXPHOS, and Pgc-1_. Thus, HDAC3 uniquely primes Ucp1 and thermogenic gene transcription to ensure immediate BAT-driven thermogenesis upon acute exposure to dangerously cold temperatures.

2017-06-14 | GSE83927 | GEO

Histone Deacetylase 3 Prepares Brown Adipose Tissue For Acute Thermogenic Challenge [ChIP-Seq, GRO-Seq]

2017-06-14 | GSE83926 | GEO

Balanced Control of Thermogenesis by Nuclear Receptor Corepressors in Brown Adipose Tissue

Project description:Brown adipose tissue (BAT) is a key thermogenic organ, whose expression of Uncoupling Protein 1 (UCP1) and ability to maintain body temperature in response to acute cold exposure requires histone deacetylase 3 (HDAC3). HDAC3 exists in tight association with nuclear receptor corepressors NCoR1 and NCoR2(also known as Silencing Mediator of Retinoid and Thyroid Receptors, or SMRT), butthe functions of NCoR1/2 in BAT have not been established.Here we report that, as expected, genetic loss of NCoR1/2 in BAT (NCoR1/2 BAT-dKO) leads to loss of HDAC3 activity. In addition, HDAC3 is no longer bound at its physiological genomic sites in the absence of NCoR1/2, leading to a shared deregulation of BAT lipid metabolism between the NCoR1/2 BAT-dKO and HDAC3 BAT KO mice. Despite these commonalities, however, loss of NCoR1/2 in BAT does not phenocopy the cold sensitivity observed in the HDAC3 BAT-KO, nor does loss of either corepressor alone. Instead, BAT lacking NCoR1/2 is inflamed, particularly with respect to the IL-17 axis that increases thermogenic capacity by enhancing innervation. Integration of BAT RNA-seq and ChIP-seq data revealed that NCoR1/2 directly regulate Mmp9, which integrates extracellular matrix remodeling and inflammation. These findings reveal pleiotropic functions of the NCoR/HDAC3 corepressor complex in BAT, such that HDAC3-independent suppression of BAT inflammation counterbalances their stimulation of HDAC3 activity in the control of thermogenesis.

2022-07-27 | GSE199808 | GEO

Elucidating the role of UCP1 and FGF21 for metabolic homeostasis in the cold

Project description:Global RNA sequencing analysis of the hypothalamus, BAT, inguinal WAT and muscle of long-term cold exposed WT, FGF21 KO, UCP1 KO and UCP1/FGF21 double KO mice

2017-08-16 | GSE99412 | GEO

Impact of UCP1 and FGF21 for the development of diet-induced obesity at standard housing temperatures

Project description:Global RNA sequencing analysis of brown fat (BAT), inguinal white fat (iWAT), liver and muscle (quadriceps) of high-fat diet fed WT, FGF21 KO, UCP1 KO and UCP1/FGF21 double KO mice.

2019-11-05 | GSE122167 | GEO

A map of the PGC-1α- and NT-PGC-1α-regulated transcriptional network in brown adipose tissue [ChIP-Seq]

Project description:Transcriptional coactivator PGC-1α and its splice variant NT-PGC-1α play crucial roles in regulating cold-induced thermogenesis in brown adipose tissue (BAT). PGC-1α and NT-PGC-1α are highly induced by cold in BAT and subsequently bind to and coactivate many different transcription factors to regulate expression of genes involved in mitochondrial biogenesis, fatty acid oxidation, respiration and thermogenesis. To identify the complete repertoire of PGC-1α and NT-PGC-1α target genes in BAT, we analyzed genome-wide DNA-binding and gene expression profiles. We find that PGC-1α-/NT-PGC-1α binding broadly associates with cold-mediated transcriptional activation. In addition to their known target genes in mitochondrial biogenesis, fatty acid oxidation, respiration and thermogenesis, PGC-1α and NT-PGC-1α target to a broad spectrum of genes involved in diverse biological pathways including ubiquitin-dependent protein catabolism, ribonucleoprotein complex biosynthesis, phospholipid biosynthesis, angiogenesis, glycogen metabolism, phosphorylation, and autophagy. Our findings expand the number of genes and biological pathways that may be regulated by PGC-1α and NT-PGC-1α and provide further insight into the transcriptional regulatory network in which PGC-1α and NT-PGC-1α coordinate a comprehensive transcriptional response in BAT in response to cold.

2018-05-22 | GSE110053 | GEO

A map of the PGC-1α- and NT-PGC-1α-regulated transcriptional network in brown adipose tissue [SAGE]

2018-05-22 | GSE110055 | GEO