m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00475)
Target Name Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA)
Synonyms
PPAR-alpha; Nuclear receptor subfamily 1 group C member 1; NR1C1; PPAR
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Gene Name PPARA
Family nuclear hormone receptor family. NR1 subfamily. {ECO:0000305}.
Function
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2. {ECO:0000269|PubMed:10195690, ECO:0000269|PubMed:24043310, ECO:0000269|PubMed:7629123, ECO:0000269|PubMed:7684926, ECO:0000269|PubMed:9556573}.
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Gene ID 5395
Uniprot ID
PPARA_HUMAN
HGNC ID
HGNC:9232
Ensembl Gene ID
ENSG00000186951
KEGG ID
hsa:5465
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
PPARA can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
Browse Regulator
Browse Disease
Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line mouse embryonic stem cells Mus musculus
Treatment: METTL3-/- ESCs
Control: Wild type ESCs
 GSE145309
Regulation
logFC: -3.42E+00
p-value: 1.41E-03
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between PPARA and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 8.50E+00 GSE60213
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Hepatic deletion of Bmal1 increases m6A mRNA methylation, particularly of Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA). Inhibition of m6A methylation via knockdown of m6A methyltransferase METTL3 decreases PPaR-Alpha m6A abundance and increases PPaRalpha mRNA lifetime and expression, reducing lipid accumulation in cells in vitro. YTHDF2 binds to PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Transcriptional regulation of circadian rhythms is essential for lipid metabolic homeostasis, disruptions of which can lead to metabolic diseases.
Target Regulation Down regulation
Responsed Disease Metabolic disorders ICD-11: 5D2Z
 Disease Info 
Pathway Response PPAR signaling pathway hsa03320
Adipocytokine signaling pathway hsa04920
Cell Process Llipid metabolism
In-vitro Model Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Hepa 1-6 Hepatocellular carcinoma of the mouse Mus musculus CVCL_0327
In-vivo Model Liver-specific Bmal1f/f-AlbCre-knockout mice were purchased from Jackson Laboratory. C57BI/6J or Bmal1f/f-AlbCre-knockout male mice were maintained under a 12 hr light/12 hr dark (LD) cycle (ZT0 = 6 AM) and fed ad libitum with normal rodent chow (2018 Global 18% Protein diet, Envigo) and water. At 10-14 weeks of age, 10 male mice per group were sacrificed via CO2 asphyxiation at Zeitgeber Time (ZT) 0,2,6,10,12,14,18,22. In order to induce high levels of ROS in the liver, WT male mice were fasted 12 h and followed by intraperitoneal injection with 300 mg/kg APAP dissolved in PBS and re-fed.
YTH domain-containing family protein 2 (YTHDF2) [READER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by YTHDF2
Cell Line GSC11 cell line Homo sapiens
Treatment: siYTHDF2 GSC11 cells
Control: siControl GSC11 cells
 GSE142825
Regulation
logFC: 7.24E-01
p-value: 8.81E-04
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between PPARA and the regulator
Cell Line Hela Homo sapiens
Regulation logFC: 1.45E+00 GSE49339
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Hepatic deletion of Bmal1 increases m6A mRNA methylation, particularly of Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA). Inhibition of m6A methylation via knockdown of m6A methyltransferase METTL3 decreases PPaR-Alpha m6A abundance and increases PPaRalpha mRNA lifetime and expression, reducing lipid accumulation in cells in vitro. YTHDF2 binds to PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Transcriptional regulation of circadian rhythms is essential for lipid metabolic homeostasis, disruptions of which can lead to metabolic diseases.
Target Regulation Down regulation
Responsed Disease Metabolic disorders ICD-11: 5D2Z
 Disease Info 
Pathway Response PPAR signaling pathway hsa03320
Adipocytokine signaling pathway hsa04920
Cell Process Llipid metabolism
In-vitro Model Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Hepa 1-6 Hepatocellular carcinoma of the mouse Mus musculus CVCL_0327
In-vivo Model Liver-specific Bmal1f/f-AlbCre-knockout mice were purchased from Jackson Laboratory. C57BI/6J or Bmal1f/f-AlbCre-knockout male mice were maintained under a 12 hr light/12 hr dark (LD) cycle (ZT0 = 6 AM) and fed ad libitum with normal rodent chow (2018 Global 18% Protein diet, Envigo) and water. At 10-14 weeks of age, 10 male mice per group were sacrificed via CO2 asphyxiation at Zeitgeber Time (ZT) 0,2,6,10,12,14,18,22. In order to induce high levels of ROS in the liver, WT male mice were fasted 12 h and followed by intraperitoneal injection with 300 mg/kg APAP dissolved in PBS and re-fed.
Metabolic disorders [ICD-11: 5D2Z]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Hepatic deletion of Bmal1 increases m6A mRNA methylation, particularly of Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA). Inhibition of m6A methylation via knockdown of m6A methyltransferase METTL3 decreases PPaR-Alpha m6A abundance and increases PPaRalpha mRNA lifetime and expression, reducing lipid accumulation in cells in vitro. YTHDF2 binds to PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Transcriptional regulation of circadian rhythms is essential for lipid metabolic homeostasis, disruptions of which can lead to metabolic diseases.
Responsed Disease Metabolic disorders [ICD-11: 5D2Z]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PPAR signaling pathway hsa03320
Adipocytokine signaling pathway hsa04920
Cell Process Llipid metabolism
In-vitro Model Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Hepa 1-6 Hepatocellular carcinoma of the mouse Mus musculus CVCL_0327
In-vivo Model Liver-specific Bmal1f/f-AlbCre-knockout mice were purchased from Jackson Laboratory. C57BI/6J or Bmal1f/f-AlbCre-knockout male mice were maintained under a 12 hr light/12 hr dark (LD) cycle (ZT0 = 6 AM) and fed ad libitum with normal rodent chow (2018 Global 18% Protein diet, Envigo) and water. At 10-14 weeks of age, 10 male mice per group were sacrificed via CO2 asphyxiation at Zeitgeber Time (ZT) 0,2,6,10,12,14,18,22. In order to induce high levels of ROS in the liver, WT male mice were fasted 12 h and followed by intraperitoneal injection with 300 mg/kg APAP dissolved in PBS and re-fed.
Experiment 2 Reporting the m6A-centered Disease Response [1]
Response Summary PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Hepatic deletion of Bmal1 increases m6A mRNA methylation, particularly of Peroxisome proliferator-activated receptor alpha (PPARalpha/PPARA). Inhibition of m6A methylation via knockdown of m6A methyltransferase METTL3 decreases PPaR-Alpha m6A abundance and increases PPaRalpha mRNA lifetime and expression, reducing lipid accumulation in cells in vitro. YTHDF2 binds to PPaRalpha to mediate its mRNA stability to regulate lipid metabolism. Transcriptional regulation of circadian rhythms is essential for lipid metabolic homeostasis, disruptions of which can lead to metabolic diseases.
Responsed Disease Metabolic disorders [ICD-11: 5D2Z]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PPAR signaling pathway hsa03320
Adipocytokine signaling pathway hsa04920
Cell Process Llipid metabolism
In-vitro Model Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Hepa 1-6 Hepatocellular carcinoma of the mouse Mus musculus CVCL_0327
In-vivo Model Liver-specific Bmal1f/f-AlbCre-knockout mice were purchased from Jackson Laboratory. C57BI/6J or Bmal1f/f-AlbCre-knockout male mice were maintained under a 12 hr light/12 hr dark (LD) cycle (ZT0 = 6 AM) and fed ad libitum with normal rodent chow (2018 Global 18% Protein diet, Envigo) and water. At 10-14 weeks of age, 10 male mice per group were sacrificed via CO2 asphyxiation at Zeitgeber Time (ZT) 0,2,6,10,12,14,18,22. In order to induce high levels of ROS in the liver, WT male mice were fasted 12 h and followed by intraperitoneal injection with 300 mg/kg APAP dissolved in PBS and re-fed.
References
Ref 1 Circadian Clock Regulation of Hepatic Lipid Metabolism by Modulation of m(6)A mRNA Methylation. Cell Rep. 2018 Nov 13;25(7):1816-1828.e4. doi: 10.1016/j.celrep.2018.10.068.