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BCL6 reinforces brown adipocyte cellular identity to preserve thermogenic fitness

ABSTRACT: BCL6 reinforces brown adipocyte cellular identity to preserve thermogenic fitness

PROVIDER: PRJNA506236 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8210390.fastq.gz	Fastqsanger.gz
	SRR8210400.fastq.gz	Fastqsanger.gz
	SRR8210410.fastq.gz	Fastqsanger.gz
	SRR8210391.fastq.gz	Fastqsanger.gz
	SRR8210401.fastq.gz	Fastqsanger.gz

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BCL6 reinforces brown adipocyte cellular identity to preserve thermogenic fitness

Project description:Brown adipose tissue (BAT) generates heat via uncoupled respiration, providing mammals with an evolutionary defense against environmental cold. Although the molecular pathways by which cold activates brown adipocytes are well understood, little is known about how BAT maintains its thermogenic capacity during adaptation to environmental warmth. Here, we identify the transcriptional repressor BCL6 as the switch for maintaining brown adipocyte cellular identity under warm conditions. Mice lacking BCL6 in their brown adipocytes display normal thermogenic responses when housed in a cool environment, but fail to maintain thermogenic fitness when housed under warm conditions. In a temperature-dependent manner, BCL6 suppresses apoptosis, fatty acid storage, and coupled respiration to maintain thermogenic competence in brown adipocytes. Enhancer analysis revealed that BCL6 reinforces brown-specific while opposing white-specific enhancers to maintain cellular identity. Thus, unlike other regulators, BCL6 is dispensable for differentiation and activation of brown adipocytes, but specifically required for their maintenance in warmth.

2019-08-29 | GSE122746 | GEO

BCL6 regulates brown adipocyte dormancy to maintain thermogenic reserve and fitness.

Project description:Brown adipocytes provide a metabolic defense against environmental cold but become dormant as mammals habituate to warm environments. Although dormancy is a regulated response in brown adipocytes to environmental warmth, its transcriptional mechanisms and functional importance are unknown. Here, we identify B cell leukemia/lymphoma 6 (BCL6) as a critical regulator of dormancy in brown adipocytes but not for their commitment, differentiation, or cold-induced activation. In a temperature-dependent manner, BCL6 suppresses apoptosis, fatty acid storage, and coupled respiration to maintain thermogenic fitness during dormancy. Mechanistically, BCL6 remodels the epigenome of brown adipocytes to enforce brown and oppose white adipocyte cellular identity. Thus, unlike other thermogenic regulators, BCL6 is specifically required for maintaining thermogenic fitness when mammals acclimate to environmental warmth.

| S-EPMC6708354 | biostudies-literature

Ablation of adipocyte BCL6 enhances subcutaneous adiposity and insulin sensitivity [ChIP-seq]

Project description:In adipocyte-specific knockout mice (Bcl6AKO), we found that Bcl6 deletion results in strikingly increased inguinal but not perigonadal adipocyte size and tissue mass in addition to marked insulin sensitivity. Genome-wide DNA binding and RNA expression analyses revealed that BCL6 controls gene networks involved in cell growth and fatty acid biosynthesis. Thus, our studies identify BCL6 as a negative regulator of subcutaneous adipose tissue expansion and metabolic health.

2019-02-26 | GSE113407 | GEO

Ablation of adipocyte BCL6 enhances subcutaneous adiposity and insulin sensitivity [RNA-seq]

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Small molecule-induced polymerization triggers degradation of BCL6

Project description:Most small-molecule protein degraders act as interface stabilizers ‘molecular glues’ between E3 ubiquitin ligases and target proteins to induce ternary complex formation and ubiquitin-dependent target protein degradation. Here we report polymerization as a novel mechanism for small molecule-induced degradation. Using functional screens in combination with molecular and biochemical assays, we found that BI-3802, which binds to the BTB domain of the oncogenic transcription factor BCL6, induces polymerization of BCL6 into regular helical structures in vitro and foci in vivo. Polymerization precedes degradation by the SIAH1 E3 ubiquitin ligase. Hereby, a VxP amino acid motif on BCL6, distal from the drug-binding BTB domain, is required for SIAH1 binding, ubiquitination and BI-3802-induced degradation. Our findings propose that small molecule-induced polymerization is not only a new modality for targeted protein degradation, but also provides synthetic biology with a tool for tunable protein polymerization and opens new avenues for future drug design.

2020-11-20 | PXD016185 | Pride

Mammary ductal epithelium controls cold-induced adipocyte thermogenic program

Project description:Mammary ductal epithelium controls cold-induced adipocyte thermogenic program

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Immediate adaption – Quantitative Proteomics of BCL6 silencing and EGFR TK inhibition

Project description:We aimed to identify the response mechanism to EGFR tyrosine kinase inhibition. A431 cells were transfected with mock siRNA or BCL6 siRNA. Cells were then treated with gefitinib. Harvesting was done at 0h, at 24h and at 48h. Two TMT10plex sets were organized as follows: TMT set1: mock 0h (3x, channels 126, 127N and 127C), mock 24h (3x, 128N, 128C and 129N), mock 48h (3x, 129C, 130N, 130C) and internal pooled standard (131) composed from equal aliquots of all samples (mock siRNA and BCL6 siRNA). TMT set2: siBCL6 0h (3x, channels 126, 127N and 127C), siBCL6 24h (3x, 128N, 128C and 129N), siBCL6 48h (3x, 129C, 130N, 130C) and the same internal pooled standard (131) as for set 1.

2020-12-09 | PXD016605 | Pride

Shared PPARα/γ target genes regulate brown adipocyte thermogenic function

Project description:Shared PPARα/γ target genes regulate brown adipocyte thermogenic function

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Bcl6-deficient regulatory T cells

Project description:gene expression data from wild-type and Bcl6-/- regulatory T cells in order to find genes regulated by Bcl6 in Treg cells FoxP3+ Tregs were sorted from wild-type (WT) and Bcl6-/- (KO) mice-- 8 samples, 2 from each type of Treg, 2 WT and 2 KO

2012-12-05 | E-GEOD-40493 | biostudies-arrayexpress

Thermogenic differentiation of adipocyte progenitors

Project description:FACS-purified adipocyte progenitors from murine subcutaneous adipose tissue were cultured under conditions promoting general adipogenic differentiation or beige/brite adipocyte differentiation (treatment with cPGI2). Time course expression profiling was performed during differentiation. In addition, some cultures of differentiated adipocytes were stimulated with norepinephrine for 3 hours. In parallel, differentiation and norepinephrine stimulation of progenitors from interscapular brown fat was performed and profiled.

2015-08-20 | E-MTAB-3693 | biostudies-arrayexpress

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