Control of Embryonic Brown Adipocyte Development by GATA6 I
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE214345 | GEO | 2023/07/19
REPOSITORIES: GEO
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Project description:Brown adipose tissue (BAT) is a thermogenic organ that protects animals against hypothermia and obesity. BAT derives from the multipotent paraxial mesoderm; however, the identity of embryonic brown fat progenitor cells and regulators of adipogenic commitment are unclear. Here, we performed single cell gene expression analyses of mesenchymal cells during mouse embryogenesis with a focus on BAT development.
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Project description:Brown adipose tissue (BAT) is a thermogenic organ that protects animals against hypothermia and obesity. BAT derives from the multipotent paraxial mesoderm; however, the identity of embryonic brown fat progenitor cells and regulators of adipogenic commitment are unclear. We identified the transcription factor GATA6 as a selective marker of brown adipogenic progenitor cells. Deletion of Gata6 in the brown fat lineage resulted in a striking loss of BAT. To gain insight into the mechanism by which GATA6 supports BAT development, we performed ChIP-seq for GATA6 from the BAT of embryonic day 15.5 embryos.
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Project description:Brown and beige fats generate heat via uncoupled respiration to defend against cold, mechanistically, through the action of a network of transcription factors and cofactors. Here we globally profiled long noncoding RNAs (lncRNAs) gene expression during thermogenic adipocyte formation and identified Brown fat lncRNA 1 (Blnc1) as a novel nuclear lncRNA that promotes brown and beige adipocyte differentiation and function by forming a feedforward regulatory loop with EBF2 to drive adipogenesis toward thermogenic phenotype. LncRNAs expression were measured in BAT and WAT from mice injected saline/CL and during brown adipocyte differentiation with two replicates using Arraystar Mouse LncRNA microarray V2.0
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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.
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Project description:Brown adipose tissue (BAT) dissipates chemical energy in the form of heat, as a defense against hypothermia and obesity. Current evidence indicates that brown adipocytes arise from Myf5+-dermotomal precursors through the action of a PRDM16-C/EBP-_ transcriptional complex; however, the underlying mechanisms that determine lineage specification and maintenance of brown adipose cells remain poorly understood. Here we study the role of euchromatic histone-lysine N-methyltransferase 1 (EHMT1), a brown fat-enriched lysine methyltransferase, as an essential enzymatic component of the PRDM16 transcriptional complex and controls brown adipose cell fate. To identify targets and function of EHMT1, we performed genome-wide gene expression profiling of BAT from control mouce (Ehmt1flox/flox), Ehmt1Myf5 KO mouse (Myf5-Cre+/-; Ehmt1flox/flox) and Ehmt1adipo KO mouse (Adipo-Cre+/-; Ehmt1flox/flox). Loss of EHMT1 in Myf5+ lineage causes a near total loss of brown fat characteristics and induces muscle-selective gene program in vivo. In addition, adipose-specific deletion of EHMT1 by Adipo-Cre leads to a marked reduction of the thermogenic and fat oxidation genes.
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