m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00524)
Target Name Transcription factor ISGF-3 components p91/p84 (Stat1)
Synonyms
Signal transducer and activator of transcription 1-alpha/beta
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Gene Name Stat1
Chromosomal Location 2q32.2
Family Transcription factor STAT family
Function
Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors. Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize and associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of IFN-stimulated genes (ISG), which drive the cell in an antiviral state. In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated. It then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes, inducing a cellular antiviral state. Becomes activated in response to KITLG/SCF and KIT signaling. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4.
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Gene ID 6772
Uniprot ID
STAT1_HUMAN
HGNC ID
HGNC:11362
Ensembl Gene ID
ENSG00000115415
KEGG ID
hsa:6772
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
Stat1 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 Raw 264.7 cell line Mus musculus
Treatment: METTL3 knockout Raw 264.7 cells
Control: Wild type Raw 264.7 cells
 GSE162248
Regulation
logFC: -7.90E-01
p-value: 1.53E-25
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between Stat1 and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 2.34E+00 GSE60213
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Mettl3 promotes oxLDL-triggered inflammation through interacting with Transcription factor ISGF-3 components p91/p84 (Stat1) protein and mRNA in RAW264.7 macrophages.
Target Regulation Up regulation
Pathway Response JAK-STAT signaling pathway hsa04630
In-vitro Model RAW 264.7 Mouse leukemia Mus musculus CVCL_0493
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Transcription factor ISGF-3 components p91/p84 (Stat1) and Irf1 mRNA via Ythdf2.
Target Regulation Down regulation
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process Immunity
In-vitro Model CT26 Mouse colon adenocarcinoma Mus musculus CVCL_7254
B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
B16-F10 Mouse melanoma Mus musculus CVCL_0159
In-vivo Model 2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Methyltransferase-like 14 (METTL14) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL14
Cell Line Embryonic stem cells Mus musculus
Treatment: METTL14 knockout mESCs
Control: Wild type mESCs
 GSE156481
Regulation
logFC: -1.12E+00
p-value: 2.46E-07
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 [2]
Response Summary In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Transcription factor ISGF-3 components p91/p84 (Stat1) and Irf1 mRNA via Ythdf2.
Target Regulation Down regulation
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process Immunity
In-vitro Model CT26 Mouse colon adenocarcinoma Mus musculus CVCL_7254
B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
B16-F10 Mouse melanoma Mus musculus CVCL_0159
In-vivo Model 2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
YTH domain-containing family protein 2 (YTHDF2) [READER]
 Regulator Info 
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary RBM4 interacts with YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) to degrade m6A modified Transcription factor ISGF-3 components p91/p84 (Stat1) mRNA, thereby regulating glycolysis and M1 macrophage polarization.
Target Regulation Down regulation
Pathway Response Glycolysis / Gluconeogenesis hsa00010
Cell Process Glycolysis
In-vitro Model RAW 264.7 Mouse leukemia Mus musculus CVCL_0493
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Transcription factor ISGF-3 components p91/p84 (Stat1) and Irf1 mRNA via Ythdf2.
Target Regulation Down regulation
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process Immunity
In-vitro Model CT26 Mouse colon adenocarcinoma Mus musculus CVCL_7254
B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
B16-F10 Mouse melanoma Mus musculus CVCL_0159
In-vivo Model 2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Colorectal cancer [ICD-11: 2B91]
 Disease Info 
In total 3 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Transcription factor ISGF-3 components p91/p84 (Stat1) and Irf1 mRNA via Ythdf2.
Responsed Disease Colorectal cancer [ICD-11: 2B91]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process Immunity
In-vitro Model CT26 Mouse colon adenocarcinoma Mus musculus CVCL_7254
B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
B16-F10 Mouse melanoma Mus musculus CVCL_0159
In-vivo Model 2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Experiment 2 Reporting the m6A-centered Disease Response [2]
Response Summary In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Transcription factor ISGF-3 components p91/p84 (Stat1) and Irf1 mRNA via Ythdf2.
Responsed Disease Colorectal cancer [ICD-11: 2B91]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process Immunity
In-vitro Model CT26 Mouse colon adenocarcinoma Mus musculus CVCL_7254
B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
B16-F10 Mouse melanoma Mus musculus CVCL_0159
In-vivo Model 2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
Experiment 3 Reporting the m6A-centered Disease Response [2]
Response Summary In colorectal cancer, Mettl3- or Mettl14-deficient tumors increased cytotoxic tumor-infiltrating CD8+ T cells and elevated secretion of IFN-gamma, Cxcl9, and Cxcl10 in tumor microenvironment in vivo. Mechanistically, Mettl3 or Mettl14 loss promoted IFN-gamma-Stat1-Irf1 signaling through stabilizing the Transcription factor ISGF-3 components p91/p84 (Stat1) and Irf1 mRNA via Ythdf2.
Responsed Disease Colorectal cancer [ICD-11: 2B91]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process Immunity
In-vitro Model CT26 Mouse colon adenocarcinoma Mus musculus CVCL_7254
B16-GM-CSF (B16-GM-CSF cell line was a kind gift from Drs. Glenn Dranoff and Michael Dougan (Dana-Farber/Harvard Cancer Center))
B16-F10 Mouse melanoma Mus musculus CVCL_0159
In-vivo Model 2 × 106 CT26 cells with knockout of Mettl3, Mettl14, Mettl3/Stat1, Mettl3/Irf1, Mettl14/Stat1, or Mettl14/Irf1 and control were suspended in 200 uL of PBS/Matrigel (Corning) (1:1) and then subcutaneously inoculated into flank of each mouse.
References
Ref 1 Mettl3 promotes oxLDL-mediated inflammation through activating STAT1 signaling. J Clin Lab Anal. 2022 Jan;36(1):e24019. doi: 10.1002/jcla.24019. Epub 2021 Nov 26.
Ref 2 m(6) A RNA methyltransferases METTL3/14 regulate immune responses to anti-PD-1 therapy. EMBO J. 2020 Oct 15;39(20):e104514. doi: 10.15252/embj.2020104514. Epub 2020 Sep 23.
Ref 3 RBM4 regulates M1 macrophages polarization through targeting STAT1-mediated glycolysis. Int Immunopharmacol. 2020 Jun;83:106432. doi: 10.1016/j.intimp.2020.106432. Epub 2020 Apr 2.