Detail Information of Transcriptional Regulations

General Information of Drug Transporter (DT)
DT ID DTD0010 Transporter Info
Gene Name SLC22A1
Transporter Name Organic cation transporter 1
Gene ID
6580
UniProt ID
O15245

Transcriptional Regulation of This DT (TSR)

TF Superclass2: Zinc-coordinating DNA-binding domains

      Class2.1: Nuclear receptors with C4 zinc fingers

Click to Show/Hide the Full List of 5 TF(s) Regulating This DT

        AR 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC22A1 gene in prostate cancer condition [1]

TF Protein Name

 Androgen receptor Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Androgen receptor (AR) has been reported to bind to the transcription of SLC22A1 gene in prostate cancer condition, which leads to an affected expression of the drug transporter Organic cation transporter 1.

        HNF4A 

Click to Show/Hide to Show 2 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC22A1 gene in health condition [2]

TF Protein Name

 Hepatocyte nuclear factor 4-alpha Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Hepatocyte nuclear factor 4-alpha (HNF4A) has been reported to bind to the transcription of SLC22A1 gene in health condition, which leads to an affected expression of the drug transporter Organic cation transporter 1.

       Transcriptional Phenomenon2

 Activation of SLC22A1 gene in hepatocellular carcinoma condition [3]

TF Protein Name

 Hepatocyte nuclear factor 4-alpha Transcription Factor Info

Studied Phenotype

 Hepatocellular carcinoma [ICD11: 2C12.02]

Tissue

 Liver

Related DT Changes

 Up regulating

Experimental Material

 Human adult hepatocellular carcinoma cells (Huh7)

Detailed Description

 Hepatocyte nuclear factor 4-alpha (HNF4A) has been reported to activate the transcription of SLC22A1 gene in hepatocellular carcinoma condition, which leads to an increased expression of the drug transporter Organic cation transporter 1.

        NR1I2 

Click to Show/Hide to Show 2 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of SLC22A1 gene in health condition [4]

TF Protein Name

 Nuclear receptor subfamily 1 group I member 2 Transcription Factor Info

Studied Phenotype

 Heallth [ICD11: N.A]

Related DT Changes

 Up regulating

Detailed Description

 Nuclear receptor subfamily 1 group I member 2 (NR1I2), influenced by the metabolite from Host unspecified microbiota, has been reported to activate the transcription of SLC22A1 gene in health condition, which leads to an increased expression of the drug transporter Organic cation transporter 1.

       Transcriptional Phenomenon2

 Repression of SLC22A1 gene in hepatoblastoma condition [5]

TF Protein Name

 Nuclear receptor subfamily 1 group I member 2 Transcription Factor Info

Studied Phenotype

 Hepatoblastoma [ICD11: 2C12.01]

Tissue

 Liver

Related DT Changes

 down regulating

Experimental Material

 Human hepatoblastoma cells (HepG2)

Detailed Description

 Nuclear receptor subfamily 1 group I member 2 (NR1I2), influenced by the metabolite from Host unspecified microbiota, has been reported to repress the transcription of SLC22A1 gene in hepatoblastoma condition, which leads to a decreased expression of the drug transporter Organic cation transporter 1.

        PPARA 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of SLC22A1 gene in hepatocellular carcinoma condition [6]

TF Protein Name

 Peroxisome proliferator-activated receptor alpha Transcription Factor Info

Studied Phenotype

 Hepatocellular carcinoma [ICD11: 2C12.02]

Tissue

 Liver

Related DT Changes

 Up regulating

Experimental Material

 FVB/N mice

Detailed Description

 Peroxisome proliferator-activated receptor alpha (PPARA) has been reported to activate the transcription of SLC22A1 gene in hepatocellular carcinoma condition, which leads to an increased expression of the drug transporter Organic cation transporter 1.

        PPARG 

Click to Show/Hide to Show 2 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of SLC22A1 gene in hepatocellular carcinoma condition [6]

TF Protein Name

 Peroxisome proliferator-activated receptor gamma Transcription Factor Info

Studied Phenotype

 Hepatocellular carcinoma [ICD11: 2C12.02]

Tissue

 Liver

Related DT Changes

 Up regulating

Experimental Material

 FVB/N mice

Detailed Description

 Peroxisome proliferator-activated receptor gamma (PPARG) has been reported to activate the transcription of SLC22A1 gene in hepatocellular carcinoma condition, which leads to an increased expression of the drug transporter Organic cation transporter 1.

       Transcriptional Phenomenon2

 Activation of SLC22A1 gene in health condition [7]

TF Protein Name

 Peroxisome proliferator-activated receptor gamma Transcription Factor Info

Studied Phenotype

 Heallth [ICD11: N.A]

Tissue

 Blood

Related DT Changes

 up regulating

Experimental Material

 Human vascular smooth muscle cells

Detailed Description

 Peroxisome proliferator-activated receptor gamma (PPARG), influenced by the exogenous rosiglitazone, has been reported to activate the transcription of SLC22A1 gene in health condition , which leads to an increased expression of the drug transporter Organic cation transporter 1.

      Class2.3: C2H2 zinc finger factors

Click to Show/Hide the Full List of 2 TF(s) Regulating This DT

        CTCF 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Direct binding to SLC22A1 gene [8]

TF Protein Name

 Transcriptional repressor CTCF Transcription Factor Info

Tissue

 Striated muscle

Related DT Changes

 Direct regulating

Experiment method

 TF-transporter regulations were collected from ChIP-Seq datasets.

Detailed Description

 Transcriptional repressor CTCF (CTCF) can directly bind to the SLC22A1 gene, which in turn affects the expression or function of the drug transporter Organic cation transporter 1.

        EGR1 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC22A1 gene in erythroleukemia condition [9]

TF Protein Name

 Early growth response protein 1 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Early growth response protein 1 (EGR1) has been reported to bind to the transcription of SLC22A1 gene in erythroleukemia condition, which leads to an affected expression of the drug transporter Organic cation transporter 1.

TF Superclass3: Helix-turn-helix domains

      Class3.3: Fork head / winged helix factors

Click to Show/Hide the Full List of 2 TF(s) Regulating This DT

        FOXA1 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Direct binding to SLC22A1 gene [10]

TF Protein Name

 Hepatocyte nuclear factor 3-alpha Transcription Factor Info

Tissue

 Breast; Liver; Lung; Pancreatic ductal; Prostate

Related DT Changes

 Direct regulating

Experiment method

 TF-transporter regulations were collected from ChIP-Seq datasets.

Detailed Description

 Hepatocyte nuclear factor 3-alpha (FOXA1) can directly bind to the SLC22A1 gene, which in turn affects the expression or function of the drug transporter Organic cation transporter 1.

        FOXA2 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC22A1 gene [2]

TF Protein Name

 Hepatocyte nuclear factor 3-beta Transcription Factor Info

Related DT Changes

 Direct regulating

Detailed Description

 Hepatocyte nuclear factor 3-beta (FOXA2) has been reported to bind to the transcription of SLC22A1 gene in . condition, which leads to an affected expression of the drug transporter Organic cation transporter 1.

TF Superclass6: Immunoglobulin fold

      Class6.2: STAT domain factors

Click to Show/Hide the Full List of 1 TF(s) Regulating This DT

        STAT3 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC22A1 gene in glioblastoma multiforme condition [11]

TF Protein Name

 Signal transducer and activator of transcription 3 Transcription Factor Info

Affected Drug/Substrate

 Temozolomide

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Signal transducer and activator of transcription 3 (STAT3) has been reported to bind to the transcription of SLC22A1 gene in glioblastoma multiforme condition, which leads to an affected expression of the drug transporter Organic cation transporter 1.

      Class6.3: p53 domain factors

Click to Show/Hide the Full List of 1 TF(s) Regulating This DT

        TP53 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC22A1 gene in health condition [12]

TF Protein Name

 Cellular tumor antigen p53 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Cellular tumor antigen p53 (TP53) has been reported to bind to the transcription of SLC22A1 gene in health condition, which leads to an affected expression of the drug transporter Organic cation transporter 1.
References
1 Inhibition of p53 expression modifies the specificity of chromatin binding by the androgen receptor. Oncotarget. 2012;3(2):183-94.
2 Molecular interactions between HNF4a, FOXA2 and GABP identified at regulatory DNA elements through ChIP-sequencing. Nucleic Acids Res. 2009;37(22):7498-508.
3 The human organic cation transporter-1 gene is transactivated by hepatocyte nuclear factor-4alpha. J Pharmacol Exp Ther. 2006 May;317(2):778-85.
4 Intestinal flora induces the expression of Cyp3a in the mouse liver. Xenobiotica. 2009 Apr;39(4):323-34.
5 The pregnane X receptor down-regulates organic cation transporter 1 (SLC22A1) in human hepatocytes by competing for ("squelching") SRC-1 coactivator. Br J Pharmacol. 2016 May;173(10):1703-15.
6 Transcriptional regulation of murine Slc22a1 (Oct1) by peroxisome proliferator agonist receptor-alpha and -gamma. Am J Physiol Gastrointest Liver Physiol. 2005 Feb;288(2):G207-12.
7 Regulation of the growth arrest and DNA damage-inducible gene 45 (GADD45) by peroxisome proliferator-activated receptor gamma in vascular smooth muscle cells. Circ Res. 2003 Aug 22;93(4):e38-47.
8 NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res. 2013 Jan;41(D1):D991-5.
9 Global analysis of in vivo EGR1-binding sites in erythroleukemia cell using chromatin immunoprecipitation and massively parallel sequencing. Electrophoresis. 2010;31(17):2936-43.
10 hTFtarget: A Comprehensive Database for Regulations of Human Transcription Factors and Their Targets. Genomics Proteomics Bioinformatics. 2020 Apr;18(2):120-406. (ID:ENSG00000175003)
11 Unique genome-wide map of TCF4 and STAT3 targets using ChIP-seq reveals their association with new molecular subtypes of glioblastoma. Neuro Oncol. 2013;15(3):279-89.
12 Genome-wide analysis of p63 binding sites identifies AP-2 factors as co-regulators of epidermal differentiation. Nucleic Acids Res. 2012;40(15):7190-206.

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