Detail Information of Transcriptional Regulations

General Information of Drug Transporter (DT)
DT ID DTD0017 Transporter Info
Gene Name ABCC6
Transporter Name Multidrug resistance-associated protein 6
Gene ID
368
UniProt ID
O95255

Transcriptional Regulation of This DT (TSR)

TF Superclass1: Basic domains

      Class1.1: Basic leucine zipper factors

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

        BACH1 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCC6 gene in breast cancer bone metastasis condition [1]

TF Protein Name

 Transcription regulator protein BACH1 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Up regulating

Detailed Description

 Transcription regulator protein BACH1 (BACH1) has been reported to activate the transcription of ABCC6 gene in breast cancer bone metastasis condition, which leads to an increased expression of the drug transporter Multidrug resistance-associated protein 6.

        NFE2L2 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCC6 gene in health condition [2]

TF Protein Name

 Nuclear factor erythroid 2-related factor 2 Transcription Factor Info

Studied Phenotype

 Heallth [ICD11: N.A]

Tissue

 Liver

Related DT Changes

 Up regulating

Experimental Material

 C57BL/6 mice

Detailed Description

 Nuclear factor erythroid 2-related factor 2 (NFE2L2) has been reported to activate the transcription of ABCC6 gene in health condition, which leads to an increased expression of the drug transporter Multidrug resistance-associated protein 6.

      Class1.2: Basic helix-loop-helix factors

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

        AHR 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCC6 gene in health condition [2]

TF Protein Name

 Aryl hydrocarbon receptor Transcription Factor Info

Studied Phenotype

 Heallth [ICD11: N.A]

Tissue

 Liver

Related DT Changes

 Up regulating

Experimental Material

 C57BL/6 mice

Detailed Description

 Aryl hydrocarbon receptor (AHR) has been reported to activate the transcription of ABCC6 gene in health condition, which leads to an increased expression of the drug transporter Multidrug resistance-associated protein 6.

        TCF4 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCC6 gene in glioblastoma multiforme condition [3]

TF Protein Name

 Transcription factor 4 Transcription Factor Info

Affected Drug/Substrate

 Temozolomide

Studied Phenotype

 .

Related DT Changes

 Up regulating

Detailed Description

 Transcription factor 4 (TCF4) has been reported to activate the transcription of ABCC6 gene in glioblastoma multiforme condition, which leads to an increased expression of the drug transporter Multidrug resistance-associated protein 6.

TF Superclass2: Zinc-coordinating DNA-binding domains

      Class2.1: Nuclear receptors with C4 zinc fingers

Click to Show/Hide the Full List of 3 TF(s) Regulating This DT

        HNF4A 

Click to Show/Hide to Show 3 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to ABCC6 gene in health condition [4]

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 ABCC6 gene in health condition, which leads to an affected expression of the drug transporter Multidrug resistance-associated protein 6.

       Transcriptional Phenomenon2

 Binding to ABCC6 gene in health condition [5]

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 ABCC6 gene in health condition, which leads to an affected expression of the drug transporter Multidrug resistance-associated protein 6.

       Transcriptional Phenomenon3

 Activation of ABCC6 gene in hepatoblastoma condition [6]

TF Protein Name

 Hepatocyte nuclear factor 4-alpha Transcription Factor Info

Studied Phenotype

 Hepatoblastoma [ICD11: 2C12.01]

Tissue

 Liver

Related DT Changes

 Up regulating

Experimental Material

 Human hepatoblastoma cells (HepG2)

Detailed Description

 Hepatocyte nuclear factor 4-alpha (HNF4A) has been reported to activate the transcription of ABCC6 gene in hepatoblastoma condition, which leads to an increased expression of the drug transporter Multidrug resistance-associated protein 6.

        NR1I3 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCC6 gene in health condition [2]

TF Protein Name

 Nuclear receptor subfamily 1 group I member 3 Transcription Factor Info

Studied Phenotype

 Heallth [ICD11: N.A]

Tissue

 Liver

Related DT Changes

 Up regulating

Experimental Material

 C57BL/6 mice

Detailed Description

 Nuclear receptor subfamily 1 group I member 3 (NR1I3) has been reported to activate the transcription of ABCC6 gene in health condition, which leads to an increased expression of the drug transporter Multidrug resistance-associated protein 6.

        PPARD 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Repression of ABCC6 gene in myofibroblast condition [7]

TF Protein Name

 Peroxisome proliferator-activated receptor delta Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Down regulating

Detailed Description

 Peroxisome proliferator-activated receptor delta (PPARD) has been reported to repress the transcription of ABCC6 gene in myofibroblast condition, which leads to a decreased expression of the drug transporter Multidrug resistance-associated protein 6.

      Class2.2: Other C4 zinc finger-type factors

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

        GATA1 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Direct binding to ABCC6 gene [8]

TF Protein Name

 Erythroid transcription factor Transcription Factor Info

Tissue

 Blood; Bone marrow; Liver

Related DT Changes

 Direct regulating

Experiment method

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

Detailed Description

 Erythroid transcription factor (GATA1) can directly bind to the ABCC6 gene, which in turn affects the expression or function of the drug transporter Multidrug resistance-associated protein 6.

      Class2.3: C2H2 zinc finger factors

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

        CTCF 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Direct binding to ABCC6 gene [9]

TF Protein Name

 Transcriptional repressor CTCF Transcription Factor Info

Tissue

 Brain

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 ABCC6 gene, which in turn affects the expression or function of the drug transporter Multidrug resistance-associated protein 6.

        EGR1 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to ABCC6 gene in erythroleukemia condition [10]

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 ABCC6 gene in erythroleukemia condition, which leads to an affected expression of the drug transporter Multidrug resistance-associated protein 6.

        PLAG1 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCC6 gene in hepatoblastoma condition [11]

TF Protein Name

 Zinc finger protein PLAG1 Transcription Factor Info

Studied Phenotype

 Hepatoblastoma [ICD11: 2C12.01]

Tissue

 Liver

Related DT Changes

 Up regulating

Experimental Material

 Human hepatoblastoma cells (HepG2)

Detailed Description

 Zinc finger protein PLAG1 (PLAG1) has been reported to activate the transcription of ABCC6 gene in hepatoblastoma condition, which leads to an increased expression of the drug transporter Multidrug resistance-associated protein 6.

        PLAGL1 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCC6 gene in hepatoblastoma condition [11]

TF Protein Name

 Zinc finger protein PLAGL1 Transcription Factor Info

Studied Phenotype

 Hepatoblastoma [ICD11: 2C12.01]

Tissue

 Liver

Related DT Changes

 Up regulating

Experimental Material

 Human hepatoblastoma cells (HepG2)

Detailed Description

 Zinc finger protein PLAGL1 (PLAGL1) has been reported to activate the transcription of ABCC6 gene in hepatoblastoma condition, which leads to an increased expression of the drug transporter Multidrug resistance-associated protein 6.

        SP1 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCC6 gene in hepatoblastoma condition [11]

TF Protein Name

 Transcription factor Sp1 Transcription Factor Info

Studied Phenotype

 Hepatoblastoma [ICD11: 2C12.01]

Tissue

 Liver

Related DT Changes

 Up regulating

Experimental Material

 Human hepatoblastoma cells (HepG2)

Detailed Description

 Transcription factor Sp1 (SP1) has been reported to activate the transcription of ABCC6 gene in hepatoblastoma condition, which leads to an increased expression of the drug transporter Multidrug resistance-associated protein 6.

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 ABCC6 gene [12]

TF Protein Name

 Hepatocyte nuclear factor 3-alpha Transcription Factor Info

Tissue

 Breast; Liver; Lung; 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 ABCC6 gene, which in turn affects the expression or function of the drug transporter Multidrug resistance-associated protein 6.

        FOXA2 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to ABCC6 gene [5]

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 ABCC6 gene in . condition, which leads to a affected expression of the drug transporter Multidrug resistance-associated protein 6.

TF Superclass4: Other all-alpha-helical DNA-binding domains

      Class4.1: High-mobility group domain factors

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

        SOX2 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCC6 gene in glioblastoma condition [13]

TF Protein Name

 Transcription factor SOX-2 Transcription Factor Info

Studied Phenotype

 Glioblastoma [ICD11: 2A00.00]

Tissue

 Brain

Related DT Changes

 Up regulating

Experimental Material

 Human glioblastoma cells (A172)

Detailed Description

 Transcription factor SOX-2 (SOX2) has been reported to activate the transcription of ABCC6 gene in glioblastoma condition, which leads to an increased expression of the drug transporter Multidrug resistance-associated protein 6.

TF Superclass6: Immunoglobulin fold

      Class6.1: Rel homology region factors

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

        RELA 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCC6 gene in fibrosarcoma condition [14]

TF Protein Name

 Transcription factor p65 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Up regulating

Detailed Description

 Transcription factor p65 (RELA) has been reported to activate the transcription of ABCC6 gene in fibrosarcoma condition, which leads to an increased expression of the drug transporter Multidrug resistance-associated protein 6.
References
1 Transcriptional network analysis identifies BACH1 as a master regulator of breast cancer bone metastasis. J Biol Chem. 2012;287(40):33533-44.
2 Induction of the multidrug resistance-associated protein family of transporters by chemical activators of receptor-mediated pathways in mouse liver. Drug Metab Dispos. 2005 Jul;33(7):956-62.
3 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.
4 Mapping of HNF4alpha target genes in intestinal epithelial cells. BMC Gastroenterol. 2009;9:68.
5 Molecular interactions between HNF4a, FOXA2 and GABP identified at regulatory DNA elements through ChIP-sequencing. Nucleic Acids Res. 2009;37(22):7498-508.
6 The ERK1/2-hepatocyte nuclear factor 4alpha axis regulates human ABCC6 gene expression in hepatocytes. J Biol Chem. 2010 Jul 23;285(30):22800-8.
7 Genomewide analyses define different modes of transcriptional regulation by peroxisome proliferator-activated receptor. PLoS One. 2011;6(1):e16344.
8 Closure of the NCBI SRA and implications for the long-term future of genomics data storage. Genome Biol. 2011;12(3):402.
9 NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res. 2013 Jan;41(D1):D991-5.
10 Global analysis of in vivo EGR1-binding sites in erythroleukemia cell using chromatin immunoprecipitation and massively parallel sequencing. Electrophoresis. 2010;31(17):2936-43.
11 The human pseudoxanthoma elasticum gene ABCC6 is transcriptionally regulated by PLAG family transcription factors. Hum Genet. 2008 Dec;124(5):451-63.
12 hTFtarget: A Comprehensive Database for Regulations of Human Transcription Factors and Their Targets. Genomics Proteomics Bioinformatics. 2020 Apr;18(2):120-176. (ID:ENSG00000091262)
13 ID4 imparts chemoresistance and cancer stemness to glioma cells by derepressing miR-9*-mediated suppression of SOX2. Cancer Res. 2011 May 1;71(9):3410-21.
14 Modulation of gene expression regulated by the transcription factor NF-B/RelA. J Biol Chem. 2014;289(17):11927-11944.

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