Detail Information of Transcriptional Regulations

General Information of Drug Transporter (DT)
DT ID DTD0013 Transporter Info
Gene Name ABCB4
Transporter Name Multidrug resistance protein 3
Gene ID
5244
UniProt ID
P21439

Transcriptional Regulation of This DT (TSR)

TF Superclass1: Basic domains

      Class1.1: Basic leucine zipper factors

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

        BACH1 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCB4 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 ABCB4 gene in breast cancer bone metastasis condition, which leads to an increased expression of the drug transporter Multidrug resistance protein 3.

        CEBPA 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Direct binding to ABCB4 gene [2]

TF Protein Name

 CCAAT/enhancer-binding protein alpha Transcription Factor Info

Tissue

 Blood

Related DT Changes

 Direct regulating

Experiment method

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

Detailed Description

 CCAAT/enhancer-binding protein alpha (CEBPA) can directly bind to the ABCB4 gene, which in turn affects the expression or function of the drug transporter Multidrug resistance protein 3.

        CEBPB 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Direct binding to ABCB4 gene [3]

TF Protein Name

 CCAAT/enhancer-binding protein beta Transcription Factor Info

Tissue

 Bone

Related DT Changes

 Direct regulating

Experiment method

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

Detailed Description

 CCAAT/enhancer-binding protein beta (CEBPB) can directly bind to the ABCB4 gene, which in turn affects the expression or function of the drug transporter Multidrug resistance protein 3.

        CREB1 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Direct binding to ABCB4 gene [3]

TF Protein Name

 Cyclic AMP-responsive element-binding protein 1 Transcription Factor Info

Tissue

 Blood; Liver

Related DT Changes

 Direct regulating

Experiment method

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

Detailed Description

 Cyclic AMP-responsive element-binding protein 1 (CREB1) can directly bind to the ABCB4 gene, which in turn affects the expression or function of the drug transporter Multidrug resistance protein 3.

        JUN 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to ABCB4 gene in K562 cells [4]

TF Protein Name

 Transcription factor Jun Transcription Factor Info

Related DT Changes

 Direct regulating

Detailed Description

 Transcription factor Jun (JUN) has been reported to bind to the transcription of ABCB4 gene in K562 cells, which leads to an affected expression of the drug transporter Multidrug resistance protein 3.

      Class1.2: Basic helix-loop-helix factors

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

        TCF4 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to ABCB4 gene in glioblastoma multiforme condition [5]

TF Protein Name

 Transcription factor 4 Transcription Factor Info

Affected Drug/Substrate

 Temozolomide

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Transcription factor 4 (TCF4) has been reported to bind to the transcription of ABCB4 gene in glioblastoma multiforme condition, which leads to an affected expression of the drug transporter Multidrug resistance protein 3.

TF Superclass2: Zinc-coordinating DNA-binding domains

      Class2.1: Nuclear receptors with C4 zinc fingers

Click to Show/Hide the Full List of 4 TF(s) Regulating This DT

        NR1H4 

Click to Show/Hide to Show 2 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCB4 gene in hepatoblastoma condition [6]

TF Protein Name

 Bile acid receptor Transcription Factor Info

Studied Phenotype

 Hepatoblastoma [ICD11: 2C12.01]

Tissue

 Liver

Related DT Changes

 Up regulating

Experimental Material

 Human hepatoblastoma cells (HepG2)

Detailed Description

 Bile acid receptor (NR1H4) has been reported to activate the transcription of ABCB4 gene in hepatoblastoma condition, which leads to an increased expression of the drug transporter Multidrug resistance protein 3.

       Transcriptional Phenomenon2

 Repression of ABCB4 gene in breast cancer condition [7]

TF Protein Name

 Bile acid receptor Transcription Factor Info

Studied Phenotype

 Breast cancer [ICD11: 2C60-2C6Z]

Tissue

 Breast

Related DT Changes

 down regulating

Experimental Material

 Human invasive breast carcinoma of no special type cells (MCF-7)

Detailed Description

 Bile acid receptor (NR1H4), influenced by the exogenous gW-4064, has been reported to repress the transcription of ABCB4 gene in breast cancer condition , which leads to a decreased expression of the drug transporter Multidrug resistance protein 3.

        PPARA 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCB4 gene in hyperlipidemia condition [8]

TF Protein Name

 Peroxisome proliferator-activated receptor alpha Transcription Factor Info

Studied Phenotype

 Hyperlipidemia [ICD11: 5C80]

Tissue

 Liver

Related DT Changes

 Up regulating

Experimental Material

 SV129 mice

Detailed Description

 Peroxisome proliferator-activated receptor alpha (PPARA) has been reported to activate the transcription of ABCB4 gene in hyperlipidemia condition, which leads to an increased expression of the drug transporter Multidrug resistance protein 3.

        PPARD 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Repression of ABCB4 gene in myofibroblasts condition [9]

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 ABCB4 gene in myofibroblasts condition, which leads to a decreased expression of the drug transporter Multidrug resistance protein 3.

        VDR 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to ABCB4 gene in THP-1 human monocytic leukemia cells condition [10]

TF Protein Name

 Vitamin D3 receptor Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Vitamin D3 receptor (VDR) has been reported to bind to the transcription of ABCB4 gene in THP-1 human monocytic leukemia cells condition, which leads to an affected expression of the drug transporter Multidrug resistance protein 3.

TF Superclass3: Helix-turn-helix domains

      Class3.3: Fork head / winged helix factors

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

        FOXA1 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Direct binding to ABCB4 gene [11]

TF Protein Name

 Hepatocyte nuclear factor 3-alpha Transcription Factor Info

Tissue

 Breast; Embryo; 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 ABCB4 gene, which in turn affects the expression or function of the drug transporter Multidrug resistance protein 3.

        FOXA2 

Click to Show/Hide to Show 2 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to ABCB4 gene in health condition [12]

TF Protein Name

 Hepatocyte nuclear factor 3-beta Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Hepatocyte nuclear factor 3-beta (FOXA2) has been reported to bind to the transcription of ABCB4 gene in health condition, which leads to an affected expression of the drug transporter Multidrug resistance protein 3.

       Transcriptional Phenomenon2

 Direct binding to ABCB4 gene [11]

TF Protein Name

 Hepatocyte nuclear factor 3-beta Transcription Factor Info

Tissue

 Colon

Related DT Changes

 Direct regulating

Experiment method

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

Detailed Description

 Hepatocyte nuclear factor 3-beta (FOXA2) can directly bind to the ABCB4 gene, which in turn affects the expression or function of the drug transporter Multidrug resistance protein 3.

        FOXP1 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Repression of ABCB4 gene in health condition [13]

TF Protein Name

 Forkhead box protein P1 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Down regulating

Detailed Description

 Forkhead box protein P1 (FOXP1) has been reported to repress the transcription of ABCB4 gene in health condition, which leads to a decreased expression of the drug transporter Multidrug resistance protein 3.

      Class3.5: Tryptophan cluster factors

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

        FLI1 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Direct binding to ABCB4 gene [14]

TF Protein Name

 Friend leukemia integration 1 transcription factor Transcription Factor Info

Tissue

 Blood; Mesenchymal; Vein

Related DT Changes

 Direct regulating

Experiment method

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

Detailed Description

 Friend leukemia integration 1 transcription factor (FLI1) can directly bind to the ABCB4 gene, which in turn affects the expression or function of the drug transporter Multidrug resistance protein 3.

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 ABCB4 gene in fibrosarcoma condition [15]

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 ABCB4 gene in fibrosarcoma condition, which leads to an increased expression of the drug transporter Multidrug resistance protein 3.

      Class6.7: Grainyhead domain factors

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

        GRHL2 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Direct binding to ABCB4 gene [14]

TF Protein Name

 Grainyhead-like protein 2 homolog Transcription Factor Info

Tissue

 Breast; Bronchus; Prostate

Related DT Changes

 Direct regulating

Experiment method

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

Detailed Description

 Grainyhead-like protein 2 homolog (GRHL2) can directly bind to the ABCB4 gene, which in turn affects the expression or function of the drug transporter Multidrug resistance protein 3.

TF Superclass7: beta-Hairpin exposed by an alpha/beta-scaffold

      Class7.1: SMAD/NF-1 DNA-binding domain factors

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

        SMAD4 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCB4 gene in human embryonic stem cells (hESCs) condition [16]

TF Protein Name

 Mothers against decapentaplegic homolog 4 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Up regulating

Detailed Description

 Mothers against decapentaplegic homolog 4 (SMAD4) has been reported to activate the transcription of ABCB4 gene in human embryonic stem cells (hESCs) condition, which leads to an increased expression of the drug transporter Multidrug resistance protein 3.
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 hTFtarget: A Comprehensive Database for Regulations of Human Transcription Factors and Their Targets. Genomics Proteomics Bioinformatics. 2020 Apr;18(2):120-133. (ID:ENSG00000005471)
3 NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res. 2013 Jan;41(D1):D991-5.
4 c-Jun binding site identification in K562 cells. J Genet Genomics. 2011;38(6):235-42.
5 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.
6 Farnesoid X receptor activates transcription of the phospholipid pump MDR3. J Biol Chem. 2003 Dec 19;278(51):51085-90.
7 The farnesoid X receptor is expressed in breast cancer and regulates apoptosis and aromatase expression. Cancer Res. 2006 Oct 15;66(20):10120-6.
8 Peroxisome proliferator-activated receptor alpha (PPARalpha)-mediated regulation of multidrug resistance 2 (Mdr2) expression and function in mice. Biochem J. 2003 Feb 1;369(Pt 3):539-47.
9 Genomewide analyses define different modes of transcriptional regulation by peroxisome proliferator-activated receptor. PLoS One. 2011;6(1):e16344.
10 Patterns of genome-wide VDR locations. PLoS One. 2014;9(4):e96105.
11 Closure of the NCBI SRA and implications for the long-term future of genomics data storage. Genome Biol. 2011;12(3):402.
12 Molecular interactions between HNF4a, FOXA2 and GABP identified at regulatory DNA elements through ChIP-sequencing. Nucleic Acids Res. 2009;37(22):7498-508.
13 An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming. Cell. 2011;147(1):132-46.
14 The Encyclopedia of DNA elements (ENCODE): data portal update. Nucleic Acids Res. 2018 Jan 4;46(D1):D794-D801
15 Modulation of gene expression regulated by the transcription factor NF-B/RelA. J Biol Chem. 2014;289(17):11927-11944.
16 Chromatin and transcriptional signatures for Nodal signaling during endoderm formation in hESCs. Dev Biol. 2011;357(2):492-504.

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