Systemic determination of PRDM16 regulatory genes in the aorta
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1139189 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29931515_1.fastq.gz | Fastqsanger.gz | |||
| SRR29931515_2.fastq.gz | Fastqsanger.gz | |||
| SRR29931516_1.fastq.gz | Fastqsanger.gz | |||
| SRR29931516_2.fastq.gz | Fastqsanger.gz | |||
| SRR29931517_1.fastq.gz | Fastqsanger.gz |
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Project description:We determined the differentially expressed genes in the thoracic aorta (TA) from vascular smooth muscle cell (VSMC)-specific Prdm16 knockout (Prdm16SMKO) and control mice by RNA-sequencing (RNA-seq) analysis. We also performed chromatin immunoprecipitation (ChIP)-sequencing (ChIP-seq) analysis to identify potential target genes of PRDM16. By overlapping the RNA-seq and ChIP-seq dataset, we are able to identify the target genes of PRDM16 in the aorta and investigate the roles of PRDM16 in the vascular biology.
2025-01-15 | GSE272891 | GEO
Project description:Abdominal aortic aneurysm (AAA) is usually asymptomatic until life-threatening complications occur, predominantly involving aortic rupture. Currently, no drug-based treatments are available, primarily due to limited understanding of AAA pathogenesis. The transcriptional regulator PR domain–containing protein 16 (PRDM16) is highly expressed in the aorta, but its functions in the aorta are largely unknown. By RNA-seq analysis, we found that vascular smooth muscle cell–specific (VSMC-specific) Prdm16-knockout (Prdm16SMKO) mice already showed extensive changes in the expression of genes associated with extracellular matrix (ECM) remodeling and inflammation in the abdominal aorta under normal housing conditions without any pathological stimuli. Human AAA lesions displayed lower PRDM16 expression. Periadventitial elastase application to the suprarenal region of the abdominal aorta aggravated AAA formation in Prdm16SMKO mice. During AAA development, VSMCs undergo apoptosis because of both intrinsic and environmental changes, including inflammation and ECM remodeling. Prdm16 deficiency promoted inflammation and apoptosis in VSMCs. A disintegrin and metalloproteinase 12 (ADAM12) is a gelatinase that can degrade various ECMs. We found that ADAM12 is a target of transcriptional repression by PRDM16. Adam12 knockdown reversed VSMC apoptosis induced by Prdm16 deficiency. Our study demonstrated that PRDM16 deficiency in VSMCs promoted ADAM12 expression and aggravates AAA formation, which may provide potential targets for AAA treatment.
2023-06-08 | GSE222440 | GEO
Project description:Mutation of the PRDM16 gene causes human dilated and noncompaction cardiomyopathy. The PRDM16 protein is a transcriptional regulator that affects cardiac development via Tbx5 and Hand1, thus regulating myocardial structure. The biallelic inactivation of Prdm16 induces severe cardiac dysfunction with postnatal lethality and hypertrophy in mice. The early pathological events that occur upon Prdm16 inactivation have not been explored. This study performed in-depth pathophysiological and molecular analyses of male and female Prdm16csp1/wt mice that carry systemic, monoallelic Prdm16 gene inactivation. We systematically assessed early molecular changes through transcriptomics, proteomics, and metabolomics. Kinetic modelling of cardiac metabolism was performed in silico with CARDIOKIN.
2023-07-21 | PXD043601 | Pride
Project description:Gene expression profile from brown adipose tissues of Prdm16 knockout and wile type mice. Prdm16 is a transcription factor that regulates the thermogenic gene program in brown and beige adipocytes. However, whether Prdm16 is required for the development or physiological function of brown adipose tissue (BAT) in vivo has been unclear. By analyzing mice that selectively lacked Prdm16 in the brown adipose lineage, we found that Prdm16 was dispensable for embryonic BAT development. Brown adipose tissues were collected from Prdm16 knockout and wiletype mice with 4 biological replicates per condition. Experiment was done in two separate batch for 6-week-old and 11-month-old. Extracted RNA was hybridized to Agilent two-color arrays.
2014-04-09 | E-GEOD-55080 | biostudies-arrayexpress
Project description:Prdm16 is a transcription factor that drives a complete program of brown adipocyte differentiation, but the mechanism by which Prdm16 activates gene transcription remains unknown. Utilizing ChIP-seq teqhnique, we found that Prdm16 binds to chromatin at/near many brown fat-selective genes in BAT. Interestingly, Prdm16-deficiency dramatically reduced the binding of Med1 to Prdm16-target sites. Indeed, Prdm16 binds and recruits Med1 to BAT-enriched genes and the loss of Prdm16 caused a fundamental change in chromatin architecture at key BAT-selective genes and also reduced transcirptional activity. Moreover, Prdm16, through its interaction with Med1, defines and regulates the activity of super-enhancers that drive the expression of cell identity genes. Together, these data demonstrate that Prdm16 drives gene transcription by recruiting Med1 to control chromatin architecture and super-enhancers. Brown adipose tissues were collected from Prdm16 knockout and wiletype 9-month-old mice and ChIP-seq was performed for Prdm16, PolII, Med1, and H3K27ac.
2015-02-10 | E-GEOD-63965 | biostudies-arrayexpress
Project description:Group 1 -- WT or PRDM16-KO ex vivo murine MLL-AF9 cells, and PRDM16-KO AF9 cells overexpressing either f-PRDM16 or s-PRDM16. Group 2 -- WT or total PRDM16-KO murine HSCs isolated from adult BM. Group 3 -- WT or total PRDM16-KO murine HSCs isolated from fetal liver. Group 4 -- WT or f-PRDM16-KO murine HSCs (expressing s-PRDM16 only) isolated from fetal liver.
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Project description:Cellular senescence is a hallmark of aging, and the accumulation of senescent cells (SnCs) accelerates the aging process and contributes to aging-related organ disorders. The PRDMs exhibit robust transcriptional regulatory activity and govern a wide range of biological processes. However, the role of PRDMs in cellular senescence and aging remain unclear. Here, we have demonstrated that PRDM16, among PRDMs, is decreased significantly in multiple organs of aged mice compared to young mice. Global Prdm16 deletion contributes to cellular senescence in various organs, including the kidney, heart, lung, brain hippocampus, stomach, and gut; subsequently leading to accelerated aging-related organ injury. Furthermore, tubular specific Prdm16 deletion aggravates irradiation induced kidney aging, and aging-related kidney disease subjected to ischemia reperfusion surgery. Exogenous PRDM16 gene delivery by lentivirus effectively attenuates cellular senescence in vitro and in vivo. Mechanistically, PRDM16 improves glutathione metabolism and inhibits oxidative DNA damage, the driving force of senescence. Especially, PRDM16 increases glutathione-S-transferase activity by upregulating the transcription of GSTM1. Transfection of GSTM1 restored cellular senescence and kidney aging caused by PRDM16 deficiency. Taken together, we provide a potential target for investigating the anti-aging therapy.
2025-08-25 | GSE275768 | GEO
Project description:PRDM16 ChIP was perfomed in control and Prdm16 KO crypts isolated from the duodenum of 6 week old mice 3 days after inducible gene deletion
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Project description:PRDM16 is highly enriched in adult stem cells and plays a crucial role in multiple developmental processes. Here we demonstrate that PRDM16 is a histone H3K4 methyltransferase and this activity is essential for PRDM16 to function as a tumor suppressor. We show that PRDM16, through its regulation of transcription factor GFI1b, antagonizes the functions of MLL fusion proteins by repressing HOXA gene expression and therefore, specifically suppresses the transformation capability of MLL-AF9, MLL-AF6 and MLL-ENL. Furthermore, overexpression of PRDM16, but not the inactive PRDM16 mutant, blocks MLL mediated leukemogenesis while PRDM16 depletion significantly shortens the disease latency in vivo. We also show that PRDM16 activity is dynamically required at the pre-leukemic stage, but not in fully transformed leukemia, depicting a little known sequence of events necessary for clonal expansion during cancer evolution. Given the importance of PRDM16 and the loss of PRDM16 methyltransferase activity in an array of human malignancies, our findings provide broad insights for PRDM16-dependent physiological and pathological processes.
2016-12-15 | GSE64218 | GEO
Project description:Cellular senescence is a hallmark of aging and the accumulation of senescent cells (SnCs) accelerates the aging process, contributing to aging-related organ disorders. The PRDF1 and RIZ1 homology domain (PRDM) protein exhibits robust transcriptional regulatory activities and governs a wide range of biological processes. However, its roles in cellular senescence remain unclear. Here, we demonstrated that PRDM16, a member of the PRDM protein family, decreased significantly in multiple organs of aged mice compared to young mice. Global Prdm16 deletion contributed to cellular senescence in various organs, including the kidneys, heart, lungs, hippocampus, stomach, and gut, leading to accelerated aging-related organ injury. Furthermore, tubular-specific Prdm16 deletion aggravated irradiation-induced kidney aging and aging-related kidney diseases in irradiated mice subjected to ischemia-reperfusion surgery. Exogenous PRDM16 gene delivery by lentivirus effectively attenuated cellular senescence in vitro and in vivo. Mechanistically, PRDM16 improved glutathione metabolism and inhibited oxidative DNA damage, which is a driving force of senescence. Specifically, PRDM16 upregulated the transcription of glutathione S-transferase mu 1 (GSTM1) by binding to its promoter region. Transfection with GSTM1 reversed PRDM16 deficiency-induced cellular senescence and kidney aging. Collectively, our results provide a potential target for the investigation of anti-aging therapies.
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