Dynamic DNA methylation landscape defines brown and white cell specificity during adipogenesis
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PROVIDER: PRJNA320124 | ENA |
REPOSITORIES: ENA
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Project description:We depicted a genome-wide integrative view of DNA methylome by reduced representation bisulfite sequencing (RRBS) and transcriptome by RNA-seq during brown and white adipocyte differentiation. Our analysis demonstrated that DNA methylation is a stable epigenetic signature for brown and white cell lineage before, during and after differentiation. When comparing white to brown adipocytes at all three time points of differentiation, we identified five members of the Hox family whose expression levels were anti-correlated with promoter methylation, suggesting a regulatory role of DNA methylation in transcription.
2017-02-07 | GSE80959 | GEO
Project description:We depicted a genome-wide integrative view of DNA methylome by reduced representation bisulfite sequencing (RRBS) and transcriptome by RNA-seq during brown and white adipocyte differentiation. Our analysis demonstrated that DNA methylation is a stable epigenetic signature for brown and white cell lineage before, during and after differentiation. When comparing white to brown adipocytes at all three time points of differentiation, we identified five members of the Hox family whose expression levels were anti-correlated with promoter methylation, suggesting a regulatory role of DNA methylation in transcription.
2017-02-07 | GSE80960 | GEO
Project description:ObjectiveDNA methylation may be a stable epigenetic contributor to defining fat cell lineage.MethodsWe performed reduced representation bisulfite sequencing (RRBS) and RNA-seq to depict a genome-wide integrative view of the DNA methylome and transcriptome during brown and white adipogenesis.ResultsOur analysis demonstrated that DNA methylation is a stable epigenetic signature for brown and white cell lineage before, during, and after differentiation. We identified 31 genes whose promoters were significantly differentially methylated between white and brown adipogenesis at all three time points of differentiation. Among them, five genes belong to the Hox family; their expression levels were anti-correlated with promoter methylation, suggesting a regulatory role of DNA methylation in transcription. Blocking DNA methylation with 5-Aza-cytidine increased the expression of these genes, with the most prominent effect on Hoxc10, a repressor of BAT marker expression.ConclusionsOur data suggest that DNA methylation may play an important role in lineage-specific development in adipocytes.
| S-EPMC5034609 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-02-07 | GSE80961 | GEO
Project description:Secreted proteins from adipose tissue play a role in metabolic cross-talk and homeostasis. We performed high sensitivity mass spectrometry-based proteomics on the cell media of human adipocytes derived from the supraclavicular brown adipose and from the subcutaneous white adipose depots of adult humans. We identified 471 potentially secreted proteins covering interesting protein categories such as hormones, growth factors, extracellular matrix proteins and proteins of the complement system, which were differentially regulated in brown and white adipocytes. A total of 101 proteins were exclusively quantified in brown adipocytes and among these were ependymin-related protein 1 (EPDR1). Functional studies suggested a role for EPDR1 in thermogenic adipogenesis. In conclusion, we report substantial differences between the secretomes of brown and white human adipocytes and identify novel candidate batokines that can be important regulators of metabolism.
2019-10-03 | PXD008541 | Pride
Project description:Attainment of a brown adipocyte cell phenotype in white adipocytes, with their abundant mitochondria and increased energy expenditure potential, is a legitimate strategy for combating obesity. The unique transcriptional regulators of the primary brown adipocyte phenotype are unknown, limiting our ability to promote brown adipogenesis over white. In the present work, we used microarray analysis strategies to study primary preadipocytes, and we made the striking discovery that brown preadipocytes demonstrate a myogenic transcriptional signature, whereas both brown and white primary preadipocytes demonstrate signatures distinct from those found in immortalized adipogenic models. We found a plausible SIRT1-related transcriptional signature during brown adipocyte differentiation that may contribute to silencing the myogenic signature. In contrast to brown preadipocytes or skeletal muscle cells, white preadipocytes express Tcf21, a transcription factor that has been shown to suppress myogenesis and nuclear receptor activity. In addition, we identified a number of developmental genes that are differentially expressed between brown and white preadipocytes and that have recently been implicated in human obesity. The interlinkage between the myocyte and the brown preadipocyte confirms the distinct origin for brown versus white adipose tissue and also represents a plausible explanation as to why brown adipocytes ultimately specialize in lipid catabolism rather than storage, much like oxidative skeletal muscle tissue. Keywords: In vitro differentiation
2007-05-31 | GSE7032 | GEO
Project description:Circular RNA Expression Profiles during brown adipogenesis
| PRJNA755181 | ENA
Project description:Increasing energy expenditure by promoting the thermogenic program in brown adipocytes is a promising approach to combat human obesity. To fully exploit the potential of this approach a comprehensive understanding of the gene regulatory network that controls both lineage commitment and differentiation of brown cells is necessary. Here, we systematically examine the transcriptomic and epigenomic transitions from mesenchymal stem cells to brown adipocytes (BA) and we perform a comparative analysis with differentiating white adipocytes (WA). We identify coding genes, lncRNA genes, and microRNA genes that are differentially regulated upon BA differentiation. In addition, we generate genome wide reference maps for several chromatin marks throughout brown adipogenesis. We identify putative (super-)enhancers, super-enhancers controlled genes in brown and white adipocytes, as well as target genes of the brown lineage-committing factor BMP7. Finally we show that overexpression and knockdown of four putative novel adipogenic regulators (the kinase Pim1, and the transcription factors Six1, Rreb1, and Sox13), indeed affects BA differentiation, suggesting an important role in brown adipogenesis.
2016-12-31 | GSE75639 | GEO
Project description:Histone H3K4me1/2 methyltransferases MLL3/MLL4 and H3K27 acetyltransferases CBP/p300 are major enhancer epigenomic writers. To understand how these epigenomic writers orchestrate enhancer landscapes during cell differentiation, we have profiled genomic binding of MLL4, CBP, lineage-determining transcription factors, as well as transcriptome and epigenome during adipogenesis of immortalized preadipocytes derived from mouse brown adipose tissue (BAT). We show that MLL4 and CBP drive the dynamic enhancer epigenome, which correlates with the dynamic transcriptome. MLL3/MLL4 are required for CBP/p300 binding on enhancers activated during adipogenesis. Further, we show that MLL4 and CBP identify super-enhancers of adipogenesis and that MLL3/MLL4 are required for the formation of super-enhancers. Finally, in brown adipocytes differentiated in culture, MLL4 identifies primed super-enhancers of genes fully activated in BAT such as the thermogenic Ucp1. Comparison of MLL4-defined super-enhancers in brown and white adipogenesis predicted a list of brown-specific super-enhancers SEs associated genes that are likely to be important to BAT functions. These results establish MLL3/MLL4 and CBP/p300 as master enhancer epigenomic writers and suggest that enhancer-priming by MLL3/MLL4 followed by enhancer-activation by CBP/p300 sequentially shape dynamic enhancer landscapes during cell differentiation. Our data also provide a rich resource for understanding epigenomic regulation of brown adipogenesis.
2017-01-01 | GSE74189 | GEO
Project description:Insulin action initiates a series of phosphorylation events regulating cellular differentiation, growth and metabolism. We have previously discovered, in a mass spectrometry-based phosphoproteomic study, that insulin/IGF-1 signaling induces phosphorylation of retinoid x receptor alpha (RXRα) at S22 in mouse brown pre-adipocytes. Here, we show that insulin induces the phosphorylation of RXRα at S22 in both brown precursor and mature adipocytes through a pathway involving ERK, downstream of IRS-1 and -2. We also found that RXRα S22 phosphorylation is promoted by insulin and upon re-feeding in brown adipose tissue in vivo, and that insulin-stimulated S22 phosphorylation of RXRα is dampened by diet-induced obesity. We used Rxra knockout cells re-expressing wild type (WT) or S22A non-phosphorylatable forms of RXRα to further characterize the role of S22 in brown adipocytes. Knockout of Rxra in brown pre-adipocytes resulted in decreased lipid accumulation and adipogenic gene expression during differentiation, and re-expression of RxraWT alleviated these effects. However, we observed no significant difference in cells re-expressing the RxraS22A mutant as compared with the cells re-expressing RxraWT. Furthermore, comparison of gene expression during adipogenesis in the WT and S22A re-expressing cells by RNA sequencing revealed similar transcriptomic profiles. Thus, our data propose a dispensable role for RXRα S22 phosphorylation in adipogenesis and transcription in differentiating brown pre-adipocytes.
2020-03-30 | GSE147687 | GEO