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Taf7l Modulates Brown Adipose Tissue Formation

ABSTRACT: Brown adipose tissue (BAT) plays an essential role in metabolic homeostasis by dissipating energy via thermogenesis through uncoupling protein 1 (Ucp1). Previously, we reported that the TATA-binding protein Associated Factor 7L (Taf7l) is an important regulator of white adipose tissue (WAT) differentiation. Here, we show that Taf7l also serves as a molecular switch between brown fat and muscle lineages in vivo and in vitro. In adipose tissue, Taf7l containing TFIID complexes associate with PPAR to mediate DNA looping between distal enhancers and core promoter elements. Our findings suggest that presence of the tissue-specific Taf7l subunit in TFIID functions to promote long-range chromatin interactions during BAT lineage specification.

ORGANISM(S): Mus musculus

PROVIDER: GSE55797 | GEO | 2014/06/03

SECONDARY ACCESSION(S): PRJNA241016

REPOSITORIES: GEO

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Taf7l Modulates Brown Adipose Tissue Formation

Project description:Brown adipose tissue (BAT) plays an essential role in metabolic homeostasis by dissipating energy via thermogenesis through uncoupling protein 1 (Ucp1). Previously, we reported that the TATA-binding protein Associated Factor 7L (Taf7l) is an important regulator of white adipose tissue (WAT) differentiation. Here, we show that Taf7l also serves as a molecular switch between brown fat and muscle lineages in vivo and in vitro. In adipose tissue, Taf7l containing TFIID complexes associate with PPAR to mediate DNA looping between distal enhancers and core promoter elements. Our findings suggest that presence of the tissue-specific Taf7l subunit in TFIID functions to promote long-range chromatin interactions during BAT lineage specification. mRNA-seq expression profiling wild type and Taf7l knockout interscapular brown adipose tissue (BAT)

2014-06-03 | E-GEOD-55797 | biostudies-arrayexpress

CRISPR/Cas9 inducible UCP1 knockout in brown adipose tissue of adult mice

Project description:Mice expressing Cas9 were administered AAV8-UCP1 sgRNA to the brown adipose tissue for inducible knockout. Mice were housed at 22ºC for two weeks and then were sacrificed. Brown adipose tissue (BAT) was harvested and RNAseq was performed to determine transcriptional changes stemming from inducible UCP1 knockout.

2021-07-01 | GSE176453 | GEO

RNA-Sequencing of wild type and UCP1-null beige adipose tissue

Project description:Since brown adipose tissue (BAT) dissipates energy through UCP1, BAT has garnered attention as a therapeutic intervention for obesity and metabolic diseases including type 2 diabetes. As we better understand the roles of classical brown and beige adipocytes, increased beige fat mass in response to a variety of external/internal cues is associated with significant improvements in glucose and lipid homeostasis that may not be entirely mediated by UCP1. We aim to analyze transcriptome of wild type and UCP1-null beige adipocyte to identify the UCP1-independent function.

2017-10-28 | E-MTAB-4085 | biostudies-arrayexpress

Sympathetic inputs regulate adaptive thermogenesis in brown adipose tissue through cAMP-Salt inducible kinase axis

Project description:Various physiological stimuli, such as cold environment, diet, and hormones, trigger brown adipose tissue (BAT) to produce heat through sympathetic nervous system (SNS)- and -adrenergic receptors (ARs). The AR stimulation increases intracellular cAMP levels through heterotrimeric G proteins and adenylate cyclases, but the processes by which cAMP modulates brown adipocyte function are not fully understood. Here we described that specific ablation of cAMP production in brown adipocytes led to reduced lipolysis, mitochondrial biogenesis, uncoupling protein 1 (Ucp1) expression, and consequently defective adaptive thermogenesis. Elevated cAMP signaling by sympathetic activation inhibited Salt-inducible kinase 2 (Sik2) through protein kinase A (PKA)-mediated phosphorylation in brown adipose tissue. Inhibition of SIKs enhanced Ucp1 expression in differentiated brown adipocytes and Sik2 knockout mice exhibited enhanced adaptive thermogenesis at thermoneutrality in an Ucp1-dependent manner. Taken together, our data indicate that suppressing Sik2 by PKA-mediated phosphorylation is a requisite for SNS-induced Ucp1 expression and adaptive thermogenesis in BAT, and targeting Sik2 may present a novel therapeutic strategy to ramp up BAT thermogenic activity in humans.

2018-07-12 | PXD009262 | Pride

Dual Functions of TAF7L in Adipocyte Differentiation

Project description:The diverse transcriptional mechanisms governing cellular differentiation and development of mammalian tissue remains poorly understood. Here we report that TAF7L, a paralogue of TFIID subunit TAF7, is enriched in adipocytes and mouse white fat tissue (WAT). Depletion of TAF7L reduced adipocyte-specific gene expression and compromised adipocyte differentiation as well as WAT development. Ectopic expression of TAF7L in myoblasts reprograms these muscle precursors into adipocytes upon induction. Genome-wide mRNA-seq expression profiling and ChIP-seq binding studies confirmed that TAF7L is required for activating adipocyte-specific genes via a dual mechanism wherein it interacts with PPARγ at enhancers and TBP/Pol II at core promoters. In vitro binding studies confirmed that TAF7L forms complexes with both TBP and PPARγ. These findings suggest that TAF7L plays an integral role in adipocyte gene expression by targeting enhancers as a cofactor for PPARγ and promoters as a component of the core transcriptional machinery.

2013-01-07 | GSE41937 | GEO

Human brown and white preadipocyes clonal dynamics predict themorgenic potential and function

Project description:Brown adipose tissue (BAT) holds therapeutic potential for obesity and metabolic syndrome via increasing energy expenditure. Both inter- and intra-individual differences contribute to heterogeneity in human BAT and potentially to differential thermogenic capacity in human populations. Here, we demonstrated the generation of brown and white preadipocyte clones from human neck fat and characterized their adipogenic differentiation and thermogenic function. Combining a UCP1 reporter system and gene expression profiling, we defined novel sets of gene signatures in human preadipocytes that could predict the thermogenic potential of mature adipocytes. Knocking out the positive UCP1 regulators, PREX1 and EDNRB, in brown preadipocytes by CRISPRs markedly abolished the high level of UCP1 in mature brown adipocytes. Finally, we showed the ability to prospectively isolate adipose progenitors with great thermogenic potential. These data provide new insights into the cellular heterogeneity in human fat and offer clinically relevant gene targets that mark thermogenically competent preadipocytes. Highly adipogenic clonal white and brown cell lines

2015-06-15 | E-GEOD-68544 | biostudies-arrayexpress

Dual Functions of TAF7L in Adipocyte Differentiation

Project description:The diverse transcriptional mechanisms governing cellular differentiation and development of mammalian tissue remains poorly understood. Here we report that TAF7L, a paralogue of TFIID subunit TAF7, is enriched in adipocytes and mouse white fat tissue (WAT). Depletion of TAF7L reduced adipocyte-specific gene expression and compromised adipocyte differentiation as well as WAT development. Ectopic expression of TAF7L in myoblasts reprograms these muscle precursors into adipocytes upon induction. Genome-wide mRNA-seq expression profiling and ChIP-seq binding studies confirmed that TAF7L is required for activating adipocyte-specific genes via a dual mechanism wherein it interacts with PPARM-NM-3 at enhancers and TBP/Pol II at core promoters. In vitro binding studies confirmed that TAF7L forms complexes with both TBP and PPARM-NM-3. These findings suggest that TAF7L plays an integral role in adipocyte gene expression by targeting enhancers as a cofactor for PPARM-NM-3 and promoters as a component of the core transcriptional machinery. Genome-wide mapping of TAF7L and additional factors, and mRNA-seq expression profiling prior to and following mouse adipocyte differentiation.

2013-01-07 | E-GEOD-41937 | biostudies-arrayexpress

Expression data from wild type and Taf7l mutant testes

Project description:TFIID is a general transcription factor required for transcription of most protein-coding genes by RNA polymerase II. TAF7L is an X-linked germ cell-specific paralogue of TAF7, which is a generally expressed component of TFIID. Here we report the generation of Taf7l mutant mice by homologous recombination in embryonic stem cells using the Cre-loxP strategy. While spermatogenesis is completed in Taf7l mutant mice, the weight of Taf7l mutant testis is decreased and the amount of sperm in the epididymis is sharply reduced. Mutant epididymal sperm exhibit abnormal morphology including folded tails. Sperm motility is significantly reduced, and Taf7l mutant males are fertile with reduced litter size. Microarray profiling reveals that the abundance of six gene transcripts (including Fscn1) in Taf7l mutant testis decreases by > 2-fold. In particular, FSCN1 is an F-action-bundling protein and thus may be critical for normal sperm morphology and sperm motility. Although deficiency of Taf7l may be compensated in part by Taf7, Taf7l has apparently evolved new specialized functions in the gene-selective transcription in male germ-cell differentiation. Our mouse studies suggest that mutations in human TAF7L gene might be implicated in X-linked oligozoospermia in men. Keywords: genetic modification

2007-08-09 | GSE5510 | GEO

Transcriptomics of FGF6-stimulated mouse brown preadipocytes

Project description:Uncoupling protein-1 (UCP1) plays a central role in energy dissipation in brown adipose tissue (BAT). Using high-throughput library screening of secreted peptides, we identified two fibroblast growth factors (FGF), FGF6 and FGF9, as novel and potent inducers of UCP1 expression in adipocytes and preadipocytes. Here we show the transcriptome of FGF6-stimulated mouse brown preadipocytes.

2020-02-07 | GSE144061 | GEO

Identification of BMP3b as a cardioprotective adipokine released by brown adipose tissue.

Project description:Brown adipose tissue (BAT) has metabolic and endocrine effects to the whole-body, secreting molecules that target different tissues. Using transcriptomic analysis from isolated BAT from mice treated with isoproterenol in WT or UCP1-knockout mice, which have disfunctional BAT, we identified Bmp3b as an adipokine produced and secreted by activated BAT.

2023-08-01 | GSE210613 | GEO

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