Detail Information of Transcriptional Regulations

General Information of Drug Transporter (DT)
DT ID DTD0232 Transporter Info
Gene Name SLC26A4
Transporter Name Sodium-independent chloride/iodide transporter
Gene ID
5172
UniProt ID
O43511

Transcriptional Regulation of This DT (TSR)

TF Superclass1: Basic domains

      Class1.1: Basic leucine zipper factors

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        CEBPB 

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       Transcriptional Phenomenon1

 Direct binding to SLC26A4 gene [1]

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 SLC26A4 gene, which in turn affects the expression or function of the drug transporter Sodium-independent chloride/iodide transporter.

      Class1.2: Basic helix-loop-helix factors

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        MYC 

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       Transcriptional Phenomenon1

 Repression of SLC26A4 gene in medulloblastoma condition [2]

TF Protein Name

 Myc proto-oncogene protein Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Down regulating

Detailed Description

 Myc proto-oncogene protein (MYC) has been reported to repress the transcription of SLC26A4 gene in medulloblastoma condition, which leads to a decreased expression of the drug transporter Sodium-independent chloride/iodide transporter.

        MYOD1 

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       Transcriptional Phenomenon1

 Direct binding to SLC26A4 gene [3]

TF Protein Name

 Myoblast determination protein 1 Transcription Factor Info

Tissue

 Myotube

Related DT Changes

 Direct regulating

Experiment method

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

Detailed Description

 Myoblast determination protein 1 (MYOD1) can directly bind to the SLC26A4 gene, which in turn affects the expression or function of the drug transporter Sodium-independent chloride/iodide transporter.

TF Superclass2: Zinc-coordinating DNA-binding domains

      Class2.3: C2H2 zinc finger factors

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        KLF9 

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       Transcriptional Phenomenon1

 Direct binding to SLC26A4 gene [3]

TF Protein Name

 Krueppel-like factor 9 Transcription Factor Info

Related DT Changes

 Direct regulating

Experiment method

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

Detailed Description

 Krueppel-like factor 9 (KLF9) can directly bind to the SLC26A4 gene, which in turn affects the expression or function of the drug transporter Sodium-independent chloride/iodide transporter.

        MAZ 

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       Transcriptional Phenomenon1

 Direct binding to SLC26A4 gene [1]

TF Protein Name

 Myc-associated zinc finger protein Transcription Factor Info

Tissue

 Blood; Lung

Related DT Changes

 Direct regulating

Experiment method

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

Detailed Description

 Myc-associated zinc finger protein (MAZ) can directly bind to the SLC26A4 gene, which in turn affects the expression or function of the drug transporter Sodium-independent chloride/iodide transporter.

TF Superclass3: Helix-turn-helix domains

      Class3.3: Fork head / winged helix factors

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        FOXI1 

Click to Show/Hide to Show 2 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC26A4 gene in Pendred syndrome condition [4]

TF Protein Name

 Forkhead box protein I1 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Forkhead box protein I1 (FOXI1) has been reported to bind to the transcription of SLC26A4 gene in Pendred syndrome condition, which leads to an affected expression of the drug transporter Sodium-independent chloride/iodide transporter.

       Transcriptional Phenomenon2

 Activation of SLC26A4 gene in hearing loss condition [5]

TF Protein Name

 Forkhead box protein I1 Transcription Factor Info

Studied Phenotype

 Hearing loss [ICD11: AB50-AB57]

Tissue

 Ear

Related DT Changes

 Up regulating

Experimental Material

 CD-1-B16 hybrid mice

Detailed Description

 Forkhead box protein I1 (FOXI1) has been reported to activate the transcription of SLC26A4 gene in hearing loss condition, which leads to an increased expression of the drug transporter Sodium-independent chloride/iodide transporter.

        mutated FOXI1 (c.103T>C) 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Repression of SLC26A4 gene in pendred syndrome condition [6]

TF Protein Name

 Forkhead box protein I1 Transcription Factor Info

Studied Phenotype

 Pendred syndrome [ICD11: 5A00.02]

Tissue

 Enlarged vestibular aqueduct

Related DT Changes

 Down regulating

Experimental Material

 human Pendred syndrome enlarged vestibular aqueduct cell isolates

Detailed Description

 mutated Forkhead box protein I1 (mutated FOXI1 (c.103T>C)) has been reported to repress the transcription of SLC26A4 gene in pendred syndrome condition, which leads to a decreased expression of the drug transporter Sodium-independent chloride/iodide transporter.

      Class3.5: Tryptophan cluster factors

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        FLI1 

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       Transcriptional Phenomenon1

 Direct binding to SLC26A4 gene [7]

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 SLC26A4 gene, which in turn affects the expression or function of the drug transporter Sodium-independent chloride/iodide transporter.

TF Superclass6: Immunoglobulin fold

      Class6.2: STAT domain factors

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        STAT6 

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       Transcriptional Phenomenon1

 Activation of SLC26A4 gene in lung cancer condition [8]

TF Protein Name

 Signal transducer and activator of transcription 6 Transcription Factor Info

Studied Phenotype

 Lung cancer [ICD11: 2C25]

Tissue

 Lung

Related DT Changes

 Up regulating

Experimental Material

 Human lung mucoepidermoid carcinoma cells (NCI-H292)

Detailed Description

 Signal transducer and activator of transcription 6 (STAT6) has been reported to activate the transcription of SLC26A4 gene in lung cancer condition, which leads to an increased expression of the drug transporter Sodium-independent chloride/iodide transporter.

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

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

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        NFIC 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Direct binding to SLC26A4 gene [9]

TF Protein Name

 Nuclear factor 1 C-type Transcription Factor Info

Tissue

 Brain; Uterus

Related DT Changes

 Direct regulating

Experiment method

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

Detailed Description

 Nuclear factor 1 C-type (NFIC) can directly bind to the SLC26A4 gene, which in turn affects the expression or function of the drug transporter Sodium-independent chloride/iodide transporter.

        SMAD4 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC26A4 gene in epithelial ovarian cancer condition [10]

TF Protein Name

 Mothers against decapentaplegic homolog 4 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Mothers against decapentaplegic homolog 4 (SMAD4) has been reported to bind to the transcription of SLC26A4 gene in epithelial ovarian cancer condition, which leads to an affected expression of the drug transporter Sodium-independent chloride/iodide transporter.
References
1 hTFtarget: A Comprehensive Database for Regulations of Human Transcription Factors and Their Targets. Genomics Proteomics Bioinformatics. 2020 Apr;18(2):120-174. (ID:ENSG00000091137)
2 Silencing of thrombospondin-1 is critical for myc-induced metastatic phenotypes in medulloblastoma. Cancer Res. 2010;70(20):8199-210.
3 NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res. 2013 Jan;41(D1):D991-5.
4 Phenotypic analyses and mutation screening of the SLC26A4 and FOXI1 genes in 101 Taiwanese families with bilateral nonsyndromic enlarged vestibular aqueduct (DFNB4) or Pendred syndrome. Audiol Neurootol. 2010;15(1):57-66.
5 Lack of pendrin expression leads to deafness and expansion of the endolymphatic compartment in inner ears of Foxi1 null mutant mice. Development. 2003 May;130(9):2013-25.
6 Transcriptional control of SLC26A4 is involved in Pendred syndrome and nonsyndromic enlargement of vestibular aqueduct (DFNB4). Am J Hum Genet. 2007 Jun;80(6):1055-63.
7 The Encyclopedia of DNA elements (ENCODE): data portal update. Nucleic Acids Res. 2018 Jan 4;46(D1):D794-D801
8 The human pendrin promoter contains two N(4) GAS motifs with different functional relevance. Cell Physiol Biochem. 2013;32(7):238-48.
9 Closure of the NCBI SRA and implications for the long-term future of genomics data storage. Genome Biol. 2011;12(3):402.
10 ChIP-seq defined genome-wide map of TGF/SMAD4 targets: implications with clinical outcome of ovarian cancer. PLoS One. 2011;6(7):e22606.

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