Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

3D chromatin contacts via HiChIP - Multimodal epigenetic and enhancer network remodeling shape the transcriptional landscape of beige adipocytes

ABSTRACT: Epigenetic regulation is a key determinant of adipocyte fate and function, conferring phenotypic plasticity to adipose tissue in response to metabolic and thermal challenges. To understand the spatiotemporal regulation of chromatin during the establishment of a beige thermogenic adipocyte phenotype, we analyzed the transcriptomic, epigenetic, and enhancer connectome dynamics during white and beige adipogenesis. Using a machine learning approach, we find that the white-specific transcriptional program is associated with promoter modulations of H3K2ac levels and chromatin accessibility. In contrast, beige-specific mitochondrial gene expression correlates with promoter changes in H3K4me3 levels. Adipocyte beiging is also mediated by a remodeling of the 3D genome involving the recruitment of short range enhancers targeting fatty acid oxidation and thermogenic genes. These increased promoter-enhancer contacts correlate with increased chromatin opening at sites enriched for C/EBP transcription factor motifs. We notably identify the C/EBP transcription factor NFIL3 as differentially bound between white and beige adipocytes at enhancers regulating PDK4, a key metabolic switch promoting fatty acid oxidation. Our results highlight a multimodal, pathway-specific regulation of the transcriptional program underlying the beige adipocyte phenotype.

ORGANISM(S): Homo sapiens

PROVIDER: GSE293135 | GEO | 2026/02/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

ATAC-seq - Multimodal epigenetic and enhancer network remodeling shape the transcriptional landscape of beige adipocytes

Project description:Epigenetic regulation is a key determinant of adipocyte fate and function, conferring phenotypic plasticity to adipose tissue in response to metabolic and thermal challenges. To understand the spatiotemporal regulation of chromatin during the establishment of a beige thermogenic adipocyte phenotype, we analyzed the transcriptomic, epigenetic, and enhancer connectome dynamics during white and beige adipogenesis. Using a machine learning approach, we find that the white-specific transcriptional program is associated with promoter modulations of H3K2ac levels and chromatin accessibility. In contrast, beige-specific mitochondrial gene expression correlates with promoter changes in H3K4me3 levels. Adipocyte beiging is also mediated by a remodeling of the 3D genome involving the recruitment of short range enhancers targeting fatty acid oxidation and thermogenic genes. These increased promoter-enhancer contacts correlate with increased chromatin opening at sites enriched for C/EBP transcription factor motifs. We notably identify the C/EBP transcription factor NFIL3 as differentially bound between white and beige adipocytes at enhancers regulating PDK4, a key metabolic switch promoting fatty acid oxidation. Our results highlight a multimodal, pathway-specific regulation of the transcriptional program underlying the beige adipocyte phenotype.

2026-02-01 | GSE293858 | GEO

Remodeling of gene regulatory networks underlying thermogenic stimuli-induced adipose beiging

Project description:Beige adipocytes are induced by cold temperatures or β3-adrenergic receptor (Adrb3) agonists. They create heat through glucose and fatty acid (FA) oxidation, conferring metabolic benefits. The distinct and shared mechanisms by which these treatments induce beiging are unknown. Here, we performed single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) on adipose tissue from mice exposed to cold or an Adrb3 agonist to identify cellular and chromatin accessibility dynamics during beiging. Both stimuli induce chromatin remodeling that influence vascularization and inflammation in adipose. Beige adipocytes from cold-exposed mice have increased accessibility at genes regulating glycolytic processes, whereas Adrb3 activation increases cAMP responses. While both thermogenic stimuli increase accessibility at genes regulating thermogenesis, lipogenesis, and beige adipocyte development, the kinetics and magnitudes of the changes are distinct for the stimuli. Accessibility changes at lipogenic genes are linked to functional changes in lipid composition of adipose. Both stimuli tend to decrease the proportion of palmitic acids, a saturated FA in adipose. However, Adrb3 activation increases the proportion of monounsaturated FAs, whereas cold increases the proportion of polyunsaturated FAs. These findings reveal common and distinct mechanisms of cold and Adrb3 induced beige adipocyte biogenesis, and identify unique functional consequences of manipulating these pathways in vivo.

2022-06-06 | GSE185377 | GEO

Single Cell RNA Profiling Reveals Adipocyte to Macrophage Signaling Sufficient to Enhance Thermogenesis

Project description:Adipocytes deficient in fatty acid synthase (iAdFASNKO) emit signals that mimic cold exposure to enhance the appearance of thermogenic beige adipocytes in mouse inguinal white adipose tissues (iWAT). Both cold- and iAdFASNKO-induced iWAT “browning” pathways upregulate the sympathetic nerve fiber (SNF) modulator Nrg4 and activate SNFs adjacent to beige adipocytes. Adipocyte cAMP/protein kinase A signaling is necessary for beige adipocyte appearance, as we show here it is blocked in Gsa deficient cold exposed or iAdFASNKO mice. Surprisingly however, denervation of iWAT failed to block adipocyte browning in iAdFASNKO mice, as it does in cold-exposed mice. Similarly, Nrg4 deficiency markedly reduced iWAT UCP1 in the cold, but not in double FASN/Nrg4 KO mice. Single-cell transcriptomic analysis of iWAT stromal cells revealed increased macrophages displaying gene expression signatures of the alternately activated type in iAdFASNKO mice, and their depletion abrogated iWAT beiging. Altogether, these findings reveal divergent cellular pathways are sufficient to cause adipocyte browning. Importantly, adipocyte signaling to enhance alternatively activated macrophages in iAdFASNKO mice is associated with enhanced adipose thermogenesis independent of the sympathetic neuron involvement this process requires in the cold.

2020-08-18 | GSE154047 | GEO

RNA-seq of cold stimulated inguinal fat of wild type and Rarres2-/- mice

Project description:Although various stimuli and mediators have been identified to promote thermogenic beige fat development, less is known about the negative regulator of cold-induced beiging. We here show that lack of chemerin that is highly expressed in white adipose tissue or its receptor CMKLR1 in adipocytes enhances cold-induced beiging and thermogenesis. Our results reveal a previously unrecognized beige-inhibitory role of chemerin-CMKLR1 axis, and suggests CMKLR1 as a therapeutic target for obesity-related metabolic disorders.

2019-12-31 | GSE133978 | GEO

Adipocyte RNA-binding protein CELF1 promotes beiging of white fat through stabilizing Dio2 mRNA

Project description:RNA-binding proteins (RBPs) regulate diverse cellular processes at post-transcriptional level and play roles in adipocyte development. However, their involvement in the beiging of white fat remains unclear. Here we screened RBPs in inguinal adipose tissues in response to cold stimulation and identified CUG-BP Elav-like family member 1 (CELF1) as a novel regulator that promotes white fat beiging. Adipocyte-specific Celf1 deficiency impairs cold-induced beiging and reduces energy expenditure. Mechanistically, RNA immunoprecipitation RNA-seq (RIP-seq) and functional experiments revealed that CELF1 stabilizes the mRNA of the key thermogenic regulator Dio2 by binding to its 3'UTR, thereby promoting local triiodothyronine (T3) production. CELF1 augments isoproterenol-induced activation of beige adipocytes and increases mitochondria respiration capacity in vitro, and CELF1 overexpression ameliorates diet-induced obesity and metabolic dysfunction. Hence, our study identifies CELF1 as a physiological regulator of metabolic stress in activating thermogenesis and promoting energy expenditure at the post-transcriptional level, suggesting that targeting CELF1 to locally increase the T3 production may serve as a promising therapeutic strategy for combating obesity and related metabolic disorders.

2025-07-05 | GSE297248 | GEO

ChIP-seq of active and repressive histone post-translational modifications in human beige and white adipocytes.

Project description:Background: The beneficial effect of thermogenic adipocytes in maintaining body weight and protecting against metabolic disorders has raised interest in understanding the regulatory mechanisms defining white and beige adipocyte identity. Although alternative splicing has been shown to propagate adipose browning signals in mice, this has yet to be thoroughly investigated in human adipocytes. Methods: We performed parallel white and beige adipogenic differentiation using primary adipose stem cells from 6 unrelated healthy subjects, and assessed differential gene and isoform expression in mature adipocytes by RNA sequencing. Results: We find 693 exon junctions with robust differential usage between white and beige adipocytes in all 6 subjects, mapping to 507 genes. Importantly, only 8% of these differentially spliced genes are also differentially expressed, indicating that alternative splicing constitutes an additional layer of gene expression regulation during beige adipocyte adipogenic differentiation. Functional classification of alternative isoforms point to a gain of function for key thermogenic regulators such as PPARG, CITED1 and PEMT. We find that a large majority of the splice variants arise from differential usage of transcription start sites (TSSs), with beige-specific TSSs being enriched for PPARγ and MED1 binding compared to white-specific TSSs. Finally, we validate beige specific isoform expression at the protein level for two thermogenic regulators, PPARγ and PEMT. Discussion: These results indicate that differential isoform expression through alternative TSS usage is an important regulatory mechanism for human adipocyte thermogenic specification.

2024-05-14 | GSE256260 | GEO

Differential junction usage in paired RNA-seq of white and beige differentiated adipocytes from six human subjects

2024-05-14 | GSE256259 | GEO

A novel GPR120-dependent pathway of control brown fat activation mediated by FGF21

Project description:Brown adipose tissue (BAT) thermogenesis and the browning of white adipose tissue are important components of energy expenditure. An RNAseq-based analysis of the mouse BAT transcriptome led us to identify GPR120 as a gene induced by thermogenic activation. GPR120, a G protein-coupled receptor binding unsaturated long-chain fatty acids, is known to mediate some beneficial metabolic actions of polyunsaturated fatty acids. We show that pharmacological activation of GPR120 induces BAT activity and promotes the browning of white fat in mice, whereas GRP120-null mice show impaired browning in response to cold. n-3 polyunsaturated fatty acids induce brown and beige adipocyte differentiation and thermogenic activation, and these effects require GPR120. GPR120 activation induces the release of fibroblast growth factor-21 (FGF-21) by brown and beige adipocytes and increases blood FGF21 levels. The effects of GPR120 activation are impaired in FGF21-null mice and cells. Thus, the lipid sensor GPR120 constitutes a novel pathway of brown fat activation and involves FGF21.

2016-12-12 | GSE77534 | GEO

ZFP423 Controls EBF2 Co-activator Recruitment and PPARgamma Occupancy to Determine the Thermogenic Plasticity of Adipocytes_ChIP-seq

Project description:Energy-storing white adipocytes maintain their identity by suppressing the gene program defining energy-burning thermogenic brown/beige adipocytes. Here, we reveal that the protein-protein interaction between the transcriptional co-regulator ZFP423 and brown/beige cell determination factor, EBF2, is essential for restraining the thermogenic phenotype of white adipose tissue (WAT). Disruption of the ZFP423-EBF2 protein interaction through CRISPR-Cas9 gene editing triggers widespread “browning” of WAT in adult mice. Mechanistically, adipocyte Zfp423 deficiency induces an EBF2 NuRD-to-BAF co-regulator switch and a shift in PPARgamma occupancy to thermogenic genes. This shift in PPARgamma occupancy increases the anti-diabetic efficacy of the PPARgamma agonist rosiglitazone in obesity while diminishing the unwanted weight-gaining effect of the drug. These data indicate that ZFP423 controls EBF2 co-activator recruitment and PPARgamma occupancy to determine the thermogenic plasticity of adipocytes and raise the concept of targeting transcriptional brakes in adipocyte gene expression as a therapeutic strategy to induce thermogenic adipocyte biogenesis in obesity.

2022-05-01 | GSE175654 | GEO

ZFP423 Controls EBF2 Co-activator Recruitment and PPARgamma Occupancy to Determine the Thermogenic Plasticity of Adipocytes_ChAP-seq

2022-05-01 | GSE175653 | GEO