DDB1 Prepares Brown Adipocytes for Cold-Induced Thermogenesis [ChIP-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA791603 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17308389_1.fastq.gz | Fastqsanger.gz | |||
| SRR17308389_2.fastq.gz | Fastqsanger.gz | |||
| SRR17308390_1.fastq.gz | Fastqsanger.gz | |||
| SRR17308390_2.fastq.gz | Fastqsanger.gz | |||
| SRR17308391_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:DDB1 Prepares Brown Adipocytes for Cold-Induced Thermogenesis
| PRJNA791617 | ENA
Project description:DDB1 Prepares Brown Adipocytes for Cold-Induced Thermogenesis [RNA-seq]
| PRJNA791619 | ENA
Project description:Adipose tissues play a pivotal role in energy homeostasis. They are existent in two forms: white adipose tissue and brown adipose tissue (BAT). Being the primary source of non-shivering thermogenesis of mammals, BAT plays an irreplaceable role in maintaining body temperature . Damaged DNA binding protein 1 (DDB1) is usually recognized as a component of the CUL4-DDB1 E3 complex. We have previously shown that DDB1 functions independently of CUL4 to promote adipogenesis. In the thesis, we focus on the function of DDB1 in mature adipocytes. We crossed Ddb1f/f mice with Adipoq-Cre or Ucp1-Cre mice to generate adipose tissue or BAT-specific mice, designated Ddb1-AKO and Ddb1-BKO mice respectively. At 8-12 weeks, BAT in these mice was servely whitened with decreased mitochdiral content. The thermogenic genes were also significantly downregulated at both RNA and protein levels. To further characterize the effect of DDB1 on thermogenesis, we first examined the bdy temperature of the pulps on postnatal day 3, and found that depletion of DDB1 caused a significant decrease in surface temperature.When the adult mice were subjected to cold challenge, both Ddb1-AKO and Ddb1-BKO mice showed dramatically decreased body temperature compared with control mice. At the end of the experiment, Ddb1-AKO and Ddb1-BKO mice had higher contents in BAT triglycerides and lower blood glucose level. Furthermore, the oxygen comsumption in Ddb1-AKO and Ddb1-BKO mice failed to respond to epinephrine injection. . All these results above demonstrated that lacking of DDB1 in brown adipocytes leads to a destruction in thermogenesis of BAT. We have also examined the phenotypes of Ddb1-AKO and Ddb1-BKO mice on high-fat-diet feeding. Compared with control mice, these mice showed decreased body weight, but significantly glucose intolerance and increased triglycierde content in liver, indicating that these mice have partial lipodystrophy. To study whether the effect of DDB1 was dependent on CUL4, we generated adipose tissue-specific Cul4a or CUl4b knockout mice, and found that these mice have no visible defect in BAT morphology compared with control mice, indicating a CUL4-independent function of DDB1. RNA-Seq analysis revealed that DDB1 is required for cold-induced expression of around 900 genes. ChIP-Seq analysis revelaed that these genes were subjected to regulation of promoter-proximally paused RNA polymerase II (Pol II), and that DDB1 is required for the release of paused Pol II upon cold stimulation. Our findings have thus revealed that DDB1 plays an important role in maintaining the theremogenic function of BAT by regulating the expression of thermogenic genes upon cold stimulation. Our studies will shed insights into transcriptional regulation of thermogenic gene
2024-12-21 | GSE192457 | GEO
Project description:Adipose tissues play a pivotal role in energy homeostasis. They are existent in two forms: white adipose tissue and brown adipose tissue (BAT). Being the primary source of non-shivering thermogenesis of mammals, BAT plays an irreplaceable role in maintaining body temperature . Damaged DNA binding protein 1 (DDB1) is usually recognized as a component of the CUL4-DDB1 E3 complex. We have previously shown that DDB1 functions independently of CUL4 to promote adipogenesis. In the thesis, we focus on the function of DDB1 in mature adipocytes. We crossed Ddb1f/f mice with Adipoq-Cre or Ucp1-Cre mice to generate adipose tissue or BAT-specific mice, designated Ddb1-AKO and Ddb1-BKO mice respectively. At 8-12 weeks, BAT in these mice was servely whitened with decreased mitochdiral content. The thermogenic genes were also significantly downregulated at both RNA and protein levels. To further characterize the effect of DDB1 on thermogenesis, we first examined the bdy temperature of the pulps on postnatal day 3, and found that depletion of DDB1 caused a significant decrease in surface temperature.When the adult mice were subjected to cold challenge, both Ddb1-AKO and Ddb1-BKO mice showed dramatically decreased body temperature compared with control mice. At the end of the experiment, Ddb1-AKO and Ddb1-BKO mice had higher contents in BAT triglycerides and lower blood glucose level. Furthermore, the oxygen comsumption in Ddb1-AKO and Ddb1-BKO mice failed to respond to epinephrine injection. . All these results above demonstrated that lacking of DDB1 in brown adipocytes leads to a destruction in thermogenesis of BAT. We have also examined the phenotypes of Ddb1-AKO and Ddb1-BKO mice on high-fat-diet feeding. Compared with control mice, these mice showed decreased body weight, but significantly glucose intolerance and increased triglycierde content in liver, indicating that these mice have partial lipodystrophy. To study whether the effect of DDB1 was dependent on CUL4, we generated adipose tissue-specific Cul4a or CUl4b knockout mice, and found that these mice have no visible defect in BAT morphology compared with control mice, indicating a CUL4-independent function of DDB1. RNA-Seq analysis revealed that DDB1 is required for cold-induced expression of around 900 genes. ChIP-Seq analysis revelaed that these genes were subjected to regulation of promoter-proximally paused RNA polymerase II (Pol II), and that DDB1 is required for the release of paused Pol II upon cold stimulation. Our findings have thus revealed that DDB1 plays an important role in maintaining the theremogenic function of BAT by regulating the expression of thermogenic genes upon cold stimulation. Our studies will shed insights into transcriptional regulation of thermogenic gene
2024-12-21 | GSE192466 | GEO
Project description:Brown adipose tissue (BAT) plays a key role in thermogenesis during acute cold exposure. However, it remains unclear how BAT is prepared to rapidly turn on thermogenic genes. Here, we show that damage-specific DNA binding protein 1 (DDB1) mediates the rapid transcription of thermogenic genes upon acute cold exposure. Adipose- or BAT-specific Ddb1 knockout mice show severely whitened BAT and significantly decreased expression of thermogenic genes. These mice develop hypothermia when subjected to acute cold exposure at 4 °C and partial lipodystrophy on a high-fat diet due to deficiency in fatty acid oxidation. Mechanistically, DDB1 binds the promoters of Ucp1 and Ppargc1a and recruits positive transcriptional elongation factor b (P-TEFb) to release promoter-proximally paused RNA polymerase II (Pol II), thereby enabling rapid and synchronized transcription of thermogenic genes upon acute cold exposure. Our findings have thus provided a regulatory mechanism of how BAT is prepared to respond to acute cold challenge.
| S-EPMC11749000 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-12-21 | GSE192467 | GEO
Project description:Insufficient mitochondrial quantity in brown adipose tissue (BAT) causes defective thermogenesis and positive energy balance, which is coupled with the development of obesity. Whether disturbance of mitochondrial quality affects BAT function remains unknown. Here, we describe that the brown adipocyte-specific Leucine-rich PPR motif-containing protein knockout mice (LrpprcBKO) exhibited mitochondrial electron transport chain (ETC) proteome imbalance and a complete loss of the -adrenergic-stimulated thermogenesis at room temperature (RT), due to specific reduction of mtDNA-encoded genes. However, the LrpprcBKO mice were lean at normal chow and were protected against high-fat-diet-induced metabolic abnormalities, such as obesity, insulin resistance, adipose inflammation, hepatic steatosis, and hypertriglyceridemia. The beige adipocytes in inguinal white adipose tissue were expanded in LrpprcBKO mice at RT, but not at thermoneutrality. However, BAT thermogenic defects and metabolic benefits were present in LrpprcBKO mice regardless of ambient temperatures. Collectively, our results reveal that a thermogenesis-incapable BAT with mitochondrial ETC proteome imbalance can improve systemic metabolism, suggesting BAT’s contributions to thermoregulation and systemic metabolism can be uncoupled.
2021-10-07 | PXD008798 | Pride
Project description:Activation of brown adipose tissue (BAT) thermogenesis increases energy expenditure and alleviates obesity. Epigenetic regulation has emerged as a key mechanism underlying BAT development and function. To study the epigenetic regulation of BAT thermogenesis, we surveyed the expression of epigenetic enzymes that catalyze histone modifications in developmental beige adipocytes and found a unique expression pattern of suppressor of variegation 4-20 homolog 2 (Drosophila) (Suv420h2), a histone methyltransferase that preferentially catalyzes the tri-methylation at histone H4 lysine 20 (H4K20me3), a hallmark of gene silencing. Here we discovered that Suv420h2 expression parallels that of UCP1 expression in brown and beige adipocytes and that SUV420H2 knockdown significantly reduces, whereas SUV420H2 overexpression significantly increases UCP1 levels in brown adipocytes. Suv420h2 knockout (H2KO mice exhibit impaired cold-induced thermogenesis and are prone to diet-induced obesity. In contrast, mice with specific overexpression of Suv420h2 in adipocytes display enhanced cold-induced thermogenesis and are resistant to diet-induced obesity. Further study showed that Suv420h2 catalyzes H4K20 trimethylation at eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) promoter, leading to down-regulated expression of 4E-BP1, a negative regulator of the translation initiation complex. This in turn up-regulates PGC1α protein levels, which is associated with increased expression of thermogenic program. We conclude that Suv420h2 is a key regulator of brown/beige adipocyte development and thermogenesis.
2024-05-09 | GSE244457 | GEO
Project description:Great progress has been made in identifying positive regulators that activate adipocyte thermogenesis, but negative regulatory signaling of thermogenesis remains poorly understood. Here, we found that cardiotrophin-like cytokine factor 1 (CLCF1) signaling led to loss of brown fat identity, which impaired thermogenic capacity. CLCF1 levels decreased during thermogenic stimulation but were considerably increased in obesity. Adipocyte-specific CLCF1 transgenic (CLCF1-ATG) mice showed impaired energy expenditure and severe cold intolerance. Elevated CLCF1 triggered whitening of brown adipose tissue by suppressing mitochondrial biogenesis. Mechanistically, CLCF1 bound and activated ciliary neurotrophic factor receptor (CNTFR) and augmented signal transducer and activator of transcription 3 (STAT3) signaling. STAT3 transcriptionally inhibited both peroxisome proliferator-activated receptor-γ coactivator (PGC) 1α and 1β, which thereafter restrained mitochondrial biogenesis in adipocytes. Inhibition of CNTFR or STAT3 could diminish the inhibitory effects of CLCF1 on mitochondrial biogenesis and thermogenesis. As a result, CLCF1-TG mice were predisposed to develop metabolic dysfunction even without external metabolic stress. Our findings revealed a previously unknown brake signal on nonshivering thermogenesis and suggested that targeting this pathway could be used to restore brown fat activity and systemic metabolic homeostasis in obesity.
2023-08-23 | GSE235476 | GEO
Project description:We found that overexpression of HOXC4 in mature adipocytes enhances thermogenesis. To investigate the binding sites of HOXC4 in the genome of brown adipocytes, we performed HOXC4 ChIP-seq experiments on differentiated primary brown adipocytes, which overexpressed HOXC4.
2025-01-22 | GSE266786 | GEO