Differentiating 3T3-L1 adipocytes, introduced with siRNA against aof2 and rfk genes, or treated with tranylcypromine
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE18598 | GEO | 2012/04/05
SECONDARY ACCESSION(S): PRJNA123791
REPOSITORIES: GEO
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Project description:Adipogenic differentiation and metabolic adaptation are initiated through transcriptional and epigenetic reprogramming. In particular, dynamic changes in histone modifications may play central roles in the rearrangement of gene expression patterns. LSD1 (KDM1) protein, encoded by aof2 gene, is a histone demethylase, which is involved in transcriptional regulation. Since the enzymatic activity of LSD1 is FAD (flavin adenine dinucleotide)-dependent, its effects on gene expression may be influenced by FAD availability. To address the importance of histone demethylation in adipogenic differentiation and function, we performed cDNA microarray in LSD1-deficient 3T3-L1 cells as well as in the cells treated with LSD1 inhibitor tranylcypromine (TC). FAD-synthesizing enyme, riboflavin kinase (RFK) -deficient cells were also subjected to the microarray analysis. 3T3-L1 preadipocytes were transfected with aof2- or rfk- specific siRNA or control siRNA (siGL3) . 24 hours later, cells were subjected to adipogenic induction. 24 hours later, cells were harvested for total RNA extraction. For the TC treatment, TC was added to the adipogenic induction medium.
2012-04-04 | E-GEOD-18598 | biostudies-arrayexpress
Project description:Adipogenic differentiation and metabolic adaptation are initiated through transcriptional and epigenetic reprogramming. In particular, dynamic changes in histone modifications may play central roles in the rearrangement of gene expression patterns. BHC80 protein, encoded by phf21a gene, is a part of LSD1 histone demethylase complex and is essential for the demethylation activity. To address the importance of histone demethylation in adipogenic differentiation and function, we performed cDNA microarray in BHC80-deficient 3T3-L1 cells 3T3-L1 preadipocytes were transfected with either BHC80-specific siRNA or control siRNA (siGL3). 24 hours later, cells were subjected to adipogenic induction. 24 hours later, cells were harvested for total RNA extraction.
2012-04-04 | E-GEOD-18599 | biostudies-arrayexpress
Project description:Adipogenic differentiation and metabolic adaptation are initiated through transcriptional and epigenetic reprogramming. In particular, dynamic changes in histone modifications may play central roles in the rearrangement of gene expression patterns. BHC80 protein, encoded by phf21a gene, is a part of LSD1 histone demethylase complex and is essential for the demethylation activity. To address the importance of histone demethylation in adipogenic differentiation and function, we performed cDNA microarray in BHC80-deficient 3T3-L1 cells
2012-04-05 | GSE18599 | GEO
Project description:Riboflavin (RF) and its cofactors (FMN and FAD) are essential molecules for vital metabolic processes in all organisms. Thus, the flavin metabolism must be tightly regulated in the cells. We previously demonstrated that the intracellular levels of flavins were tightly maintained by the enzymes involved in their synthesis and degradation, inducing a plastidic FAD hydrolase (AtNUDX23), in Arabidopsis. However, information of regulatory factors involved in the flavin homeostasis and transporters in each organelle are mostly limited. Terefore, we tried to identify novel factors involved in the flavin metabolism, such as transcription factors and transporters by a transcriptome analysis after exogenous FAD treatment.
2021-03-18 | GSE169061 | GEO
Project description:Flavin adenine dinucleotide (FAD) mediates oxidation-reduction reactions required for cellular energy demands. Fatty acid oxidation (FAO) disorders caused by flavoprotein mutations and FAD depletion disrupt energy balance and glucose production during fasting. These FAO disorders are difficult to manage clinically, and their biochemical pathogenesis is poorly understood. Here, we identify a mechanistic connection between FAD levels and hepatic glucose production. Depleting the FAD pool in mice with a vitamin B2 deficient diet (B2D) resulted in phenotypes associated with organic acidemia phenotypes, including reduced body weight and whole-body fat oxidation rates coupled with hypoglycemia. Integrated discovery approaches revealed that B2D broadly tempered fasting activation of target genes for the nuclear receptor PPARa, including those required for gluconeogenesis. Consistent with this, Ppara knockout depleted liver FAD levels and worsened B2D hepatic glucose production. Treatment with the PPARa agonist fenofibrate overcame B2D phenotypes and rescued glucose availability and fatty liver signatures through activation of the integrated stress response and refilling anaplerotic amino acid substrates for glucose production. We conclude that PPARa governs metabolic responses to FAD availability and suggest pharmacologic activation as a strategy for treating disorders of riboflavin and FAD deficiency.
2022-06-18 | GSE206200 | GEO
Project description:Riboflavin-derived molecules such as flavin mononucleotide and flavin adenine dinucleotide comprise the most important redox coenzymes all across life kingdoms. Vibrio cholerae, a pandemic diarrheagenic bacterium, is able to synthesize riboflavin through the riboflavin biosynthetic pathway (RBP) and to internalize exogenous riboflavin using the RibN importer. This bacterium thrives in different environments such as estuarine waters and the human intestinal tract. The presence of two independent riboflavin supply pathways in this species may be related to the variable riboflavin availability and requirements across different niches. In order to gain insights into the role of the riboflavin provision pathways in the physiology of V. cholerae, we analyzed the bacterial transcriptomics response to extracellular riboflavin and to the deletions of ribD (RBP-deficient strain) or ribN. Notably, many genes responding to riboflavin have been previously reported to belong to the iron regulon. Real time PCR analysis confirmed this effect and further documented that reciprocally, iron regulates RBP and ribN genes in a riboflavin-dependent way. A subset of genes were responding to both ribD and ribN deletions. Nonetheless, a group of genes was specifically affected in the ∆ribD strain, on which the functional terms protein folding and oxidation reduction process were enriched. Also, a subset of genes was affected specifically in the ∆ribN strain, on which the cytochrome complex assembly functional term was enriched. Results indicate that iron and riboflavin interrelate to regulate its respective provision genes and suggest that both common and specific effects of biosynthesized and internalized riboflavin exist.
2018-02-21 | GSE107538 | GEO
Project description:Metazoan enhancers are decorated by mono-methylation (me1) of the lysine 4 residue on histone H3 (H3K4), a mark deposited by methyltransferases MLL3/MLL4 and removed by the lysine-specific histone demethylase 1A (LSD1 or KDM1A) via its flavin adenine dinucleotide (FAD)-dependent amine oxidase activity. As a component of histone deacetylases HDAC1/2-containing complex CoREST, LSD1 is required for animal development, and is implicated in Kabuki Syndrome-like congenital diseases and multiple types of cancer. Although prior research has investigated the demethylase function of LSD1 extensively, the mechanisms underlying LSD1’s role in development and diseases remain enigmatic. Here, we have utilized genetic, epigenetic, genomic, and cell biology approaches to dissect the role of LSD1 and its demethylase activity in gene regulation and cell fate transition. Surprisingly, the catalytic inactivation of LSD1 only has a mild impact on gene expression whereas the loss of LSD1 protein de-represses enhancers globally. Moreover, LSD1 deletion, rather than its catalytic inactivation, causes defects in spontaneous differentiation, the transition from naive to primed pluripotency, embryoid body formation, and cardiomyocyte differentiation. Interestingly, deletion of LSD1 increases H3K27ac levels and binding of P300 to LSD1-targeted enhancers. We further show that the gain in the level of H3K27ac catalyzed by P300/CBP, not the loss of CoREST complex components from chromatin, contributes to the transcription de-repression of LSD1 targets and differentiation defects caused by LSD1 loss. Taken together, our study demonstrates a demethylase-independent role of LSD1 in regulating enhancers and cell fate transition, providing insight into the treatment of diseases driven by LSD1 mutations and misregulation.
2023-07-06 | GSE232253 | GEO
Project description:Metazoan enhancers are decorated by mono-methylation (me1) of the lysine 4 residue on histone H3 (H3K4), a mark deposited by methyltransferases MLL3/MLL4 and removed by the lysine-specific histone demethylase 1A (LSD1 or KDM1A) via its flavin adenine dinucleotide (FAD)-dependent amine oxidase activity. As a component of histone deacetylases HDAC1/2-containing complex CoREST, LSD1 is required for animal development, and is implicated in Kabuki Syndrome-like congenital diseases and multiple types of cancer. Although prior research has investigated the demethylase function of LSD1 extensively, the mechanisms underlying LSD1’s role in development and diseases remain enigmatic. Here, we have utilized genetic, epigenetic, genomic, and cell biology approaches to dissect the role of LSD1 and its demethylase activity in gene regulation and cell fate transition. Surprisingly, the catalytic inactivation of LSD1 only has a mild impact on gene expression whereas the loss of LSD1 protein de-represses enhancers globally. Moreover, LSD1 deletion, rather than its catalytic inactivation, causes defects in spontaneous differentiation, the transition from naive to primed pluripotency, embryoid body formation, and cardiomyocyte differentiation. Interestingly, deletion of LSD1 increases H3K27ac levels and binding of P300 to LSD1-targeted enhancers. We further show that the gain in the level of H3K27ac catalyzed by P300/CBP, not the loss of CoREST complex components from chromatin, contributes to the transcription de-repression of LSD1 targets and differentiation defects caused by LSD1 loss. Taken together, our study demonstrates a demethylase-independent role of LSD1 in regulating enhancers and cell fate transition, providing insight into the treatment of diseases driven by LSD1 mutations and misregulation.
2023-07-06 | GSE232252 | GEO
Project description:Metazoan enhancers are decorated by mono-methylation (me1) of the lysine 4 residue on histone H3 (H3K4), a mark deposited by methyltransferases MLL3/MLL4 and removed by the lysine-specific histone demethylase 1A (LSD1 or KDM1A) via its flavin adenine dinucleotide (FAD)-dependent amine oxidase activity. As a component of histone deacetylases HDAC1/2-containing complex CoREST, LSD1 is required for animal development, and is implicated in Kabuki Syndrome-like congenital diseases and multiple types of cancer. Although prior research has investigated the demethylase function of LSD1 extensively, the mechanisms underlying LSD1’s role in development and diseases remain enigmatic. Here, we have utilized genetic, epigenetic, genomic, and cell biology approaches to dissect the role of LSD1 and its demethylase activity in gene regulation and cell fate transition. Surprisingly, the catalytic inactivation of LSD1 only has a mild impact on gene expression whereas the loss of LSD1 protein de-represses enhancers globally. Moreover, LSD1 deletion, rather than its catalytic inactivation, causes defects in spontaneous differentiation, the transition from naive to primed pluripotency, embryoid body formation, and cardiomyocyte differentiation. Interestingly, deletion of LSD1 increases H3K27ac levels and binding of P300 to LSD1-targeted enhancers. We further show that the gain in the level of H3K27ac catalyzed by P300/CBP, not the loss of CoREST complex components from chromatin, contributes to the transcription de-repression of LSD1 targets and differentiation defects caused by LSD1 loss. Taken together, our study demonstrates a demethylase-independent role of LSD1 in regulating enhancers and cell fate transition, providing insight into the treatment of diseases driven by LSD1 mutations and misregulation.
2023-07-06 | GSE232250 | GEO
Project description:Genes encoding dodecin proteins are present in almost 20% of archaeal and in more than 50% of bacterial genomes. Archaeal dodecins bind riboflavin (vitamin B2), are thought to play a role in flavin homeostasis and possibly also help to protect cells from radical or oxygenic stress. Bacterial dodecins were found to bind riboflavin-5’-phosphate (also called flavin mononucleotide or FMN) and coenzyme A, but their physiological function remained unknown. In this study, we set out to investigate the relevance of dodecins for flavin metabolism and oxidative stress management in the phylogenetically related bacteria Streptomyces coelicolor and Streptomyces davawensis. Therfore we have treated Streptomyces coelicolor wildtype, Streptomyces davawensis wildytype and Streptomyces davawensis dodecin deletion strain with plumbagin, a compound, which induces oxidative stress in exponential and stationary growth phase and analysed the transcriptome via RNA-seq (Illumina TruSeq stranded mRNA libraries sequenced on Illumina HiSeq rapid mode 2 x 70nt PE).
2018-04-07 | E-MTAB-6633 | biostudies-arrayexpress