m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00373)
Target Name PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A)
Synonyms
PGC-1-alpha; PPAR-gamma coactivator 1-alpha; PPARGC-1-alpha; Ligand effect modulator 6; LEM6; PGC1; PGC1A; PPARGC1
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Gene Name PPARGC1A
Chromosomal Location 4p15.2
Function
Transcriptional coactivator for steroid receptors and nuclear receptors. Greatly increases the transcriptional activity of PPARG and thyroid hormone receptor on the uncoupling protein promoter. Can regulate key mitochondrial genes that contribute to the program of adaptive thermogenesis. Plays an essential role in metabolic reprogramming in response to dietary availability through coordination of the expression of a wide array of genes involved in glucose and fatty acid metabolism. Induces the expression of PERM1 in the skeletal muscle in an ESRRA-dependent manner. Also involved in the integration of the circadian rhythms and energy metabolism. Required for oscillatory expression of clock genes, such as ARNTL/BMAL1 and NR1D1, through the coactivation of RORA and RORC, and metabolic genes, such as PDK4 and PEPCK.
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Gene ID 10891
Uniprot ID
PRGC1_HUMAN
HGNC ID
HGNC:9237
Ensembl Gene ID
ENSG00000109819
KEGG ID
hsa:10891
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
PPARGC1A 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
Fat mass and obesity-associated protein (FTO) [ERASER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by FTO
Cell Line 253J cell line Homo sapiens
Treatment: siFTO 253J cells
Control: 253J cells
 GSE150239
Regulation
logFC: 4.58E+00
p-value: 7.10E-03
More Results Click to View More RNA-seq Results
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary FTO plays a critical anti-tumorigenic role in Clear Cell Renal Cell Carcinoma.Restored expression of FTO, through reducing m6A levels in mRNA transcripts of its critical target gene PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A), increases mitochondrial content, ROS production and oxidative damage, with the most important effect of repressed tumour growth.
Target Regulation Up regulation
Responsed Disease Renal cell carcinoma of kidney ICD-11: 2C90.0
 Disease Info 
Cell Process Oxidative stress
ROS production
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
769-P Renal cell carcinoma Homo sapiens CVCL_1050
786-O Renal cell carcinoma Homo sapiens CVCL_1051
In-vivo Model Five- to 6-week-old male athymic nude mice purchased by Charles River were used for the xenograft model. 769-P cells stably expressing Ctrl, FTO and FTO-mut were trypsinized and washed twice to thrice with standardized PBS, and then, 5 × 106 cells in 100 uL of PBS was subcutaneously injected into the flanks of the mice (five mice per group). Mice were monitored twice every week for tumour growth, and tumour diameters were measured using a caliper.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary FTO downregulation suppressed mitochondria biogenesis and energy production, showing as the decreased mitochondria mass and mitochondrial DNA (mtDNA) content, the downregulated expression of mtDNA-encoding genes and PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A) gene, together with declined ATP level. These findings provide the first evidence for the contribution of FTO for skeletal muscle differentiation.
Target Regulation Up regulation
Responsed Disease Muscular dystrophies ICD-11: 8C70
 Disease Info 
Cell Process Myogenic differentiation
mTOR signaling pathway (hsa04150)
In-vitro Model MPM (Mouse primary myoblasts from about 10-day-old C57BL/6J were isolated)
C2C12 Normal Mus musculus CVCL_0188
HEK293-FT Normal Homo sapiens CVCL_6911
In-vivo Model To generate doxycycline-inducible skeletal muscle-specific FTO deletion mice, FTOflox/flox mice were crossed with HSA-Cre mice to generate FTOflox/+ HSA-Cre mice, which were then crossed to FTOflox/flox mice to generate FTOflox/flox and FTOflox/flox HSA-Cre mice.
Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line MOLM-13 cell line Homo sapiens
Treatment: shMETTL3 MOLM13 cells
Control: MOLM13 cells
 GSE98623
Regulation
logFC: -3.59E+00
p-value: 8.55E-10
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. The expression of Acc1, Acly, Dgat2, Ehhadh, Fasn, Foxo, PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A) and Sirt1, which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.
Target Regulation Up regulation
Responsed Disease Type 2 diabetes mellitus ICD-11: 5A11
 Disease Info 
Pathway Response Insulin resistance hsa04931
Cell Process Lipid metabolism
In-vitro Model Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
In-vivo Model Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3 fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were used for experiments.
Renal cell carcinoma [ICD-11: 2C90]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary FTO plays a critical anti-tumorigenic role in Clear Cell Renal Cell Carcinoma.Restored expression of FTO, through reducing m6A levels in mRNA transcripts of its critical target gene PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A), increases mitochondrial content, ROS production and oxidative damage, with the most important effect of repressed tumour growth.
Responsed Disease Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
Cell Process Oxidative stress
ROS production
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
769-P Renal cell carcinoma Homo sapiens CVCL_1050
786-O Renal cell carcinoma Homo sapiens CVCL_1051
In-vivo Model Five- to 6-week-old male athymic nude mice purchased by Charles River were used for the xenograft model. 769-P cells stably expressing Ctrl, FTO and FTO-mut were trypsinized and washed twice to thrice with standardized PBS, and then, 5 × 106 cells in 100 uL of PBS was subcutaneously injected into the flanks of the mice (five mice per group). Mice were monitored twice every week for tumour growth, and tumour diameters were measured using a caliper.
Type 2 diabetes mellitus [ICD-11: 5A11]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. The expression of Acc1, Acly, Dgat2, Ehhadh, Fasn, Foxo, PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A) and Sirt1, which are critical to the regulation of fatty acid synthesis and oxidation were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice.
Responsed Disease Type 2 diabetes mellitus [ICD-11: 5A11]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Insulin resistance hsa04931
Cell Process Lipid metabolism
In-vitro Model Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
In-vivo Model Hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were generated by crossing mice with TBG-Cre Tg mice. METTL3 flox (METTL3 fl/fl) and hepatocyte-specific METTL3 knockout mice (TBG-Cre, METTL3 fl/fl) were used for experiments.
Muscular dystrophies [ICD-11: 8C70]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary FTO downregulation suppressed mitochondria biogenesis and energy production, showing as the decreased mitochondria mass and mitochondrial DNA (mtDNA) content, the downregulated expression of mtDNA-encoding genes and PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A) gene, together with declined ATP level. These findings provide the first evidence for the contribution of FTO for skeletal muscle differentiation.
Responsed Disease Muscular dystrophies [ICD-11: 8C70]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
Cell Process Myogenic differentiation
mTOR signaling pathway (hsa04150)
In-vitro Model MPM (Mouse primary myoblasts from about 10-day-old C57BL/6J were isolated)
C2C12 Normal Mus musculus CVCL_0188
HEK293-FT Normal Homo sapiens CVCL_6911
In-vivo Model To generate doxycycline-inducible skeletal muscle-specific FTO deletion mice, FTOflox/flox mice were crossed with HSA-Cre mice to generate FTOflox/+ HSA-Cre mice, which were then crossed to FTOflox/flox mice to generate FTOflox/flox and FTOflox/flox HSA-Cre mice.
References
Ref 1 N6-methyladenosine demethylase FTO suppresses clear cell renal cell carcinoma through a novel FTO-PGC-1Alpha signalling axis. J Cell Mol Med. 2019 Mar;23(3):2163-2173. doi: 10.1111/jcmm.14128. Epub 2019 Jan 16.
Ref 2 FTO is required for myogenesis by positively regulating mTOR-PGC-1Alpha pathway-mediated mitochondria biogenesis. Cell Death Dis. 2017 Mar 23;8(3):e2702. doi: 10.1038/cddis.2017.122.
Ref 3 METTL3 inhibits hepatic insulin sensitivity via N6-methyladenosine modification of Fasn mRNA and promoting fatty acid metabolism. Biochem Biophys Res Commun. 2019 Oct 8;518(1):120-126. doi: 10.1016/j.bbrc.2019.08.018. Epub 2019 Aug 10.