m6A Regulator Information

General Information of the m6A Regulator (ID: REG00011)
Regulator Name ETS-related transcription factor Elf-3 (ELF3)
Synonyms
E74-like factor 3; Epithelial-restricted with serine box; Epithelium-restricted Ets protein ESX; Epithelium-specific Ets transcription factor 1; ESE-1; ERT; ESX; JEN
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Gene Name ELF3
Sequence
MAATCEISNIFSNYFSAMYSSEDSTLASVPPAATFGADDLVLTLSNPQMSLEGTEKASWL
GEQPQFWSKTQVLDWISYQVEKNKYDASAIDFSRCDMDGATLCNCALEELRLVFGPLGDQ
LHAQLRDLTSSSSDELSWIIELLEKDGMAFQEALDPGPFDQGSPFAQELLDDGQQASPYH
PGSCGAGAPSPGSSDVSTAGTGASRSSHSSDSGGSDVDLDPTDGKLFPSDGFRDCKKGDP
KHGKRKRGRPRKLSKEYWDCLEGKKSKHAPRGTHLWEFIRDILIHPELNEGLMKWENRHE
GVFKFLRSEAVAQLWGQKKKNSNMTYEKLSRAMRYYYKREILERVDGRRLVYKFGKNSSG
WKEEEVLQSRN
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Family ETS family
Function
Transcriptional activator that binds and transactivates ETS sequences containing the consensus nucleotide core sequence GGA[AT]. Acts synergistically with POU2F3 to transactivate the SPRR2A promoter and with RUNX1 to transactivate the ANGPT1 promoter. Also transactivates collagenase, CCL20, CLND7, FLG, KRT8, NOS2, PTGS2, SPRR2B, TGFBR2 and TGM3 promoters. Represses KRT4 promoter activity. Involved in mediating vascular inflammation. May play an important role in epithelial cell differentiation and tumorigenesis. May be a critical downstream effector of the ERBB2 signaling pathway. May be associated with mammary gland development and involution. Plays an important role in the regulation of transcription with TATA-less promoters in preimplantation embryos, which is essential in preimplantation development (By similarity).
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Gene ID 1999
Uniprot ID
ELF3_HUMAN
Regulator Type WRITER ERASER READER
Mechanism Diagram Click to View the Original Diagram
Full List of Target Gene(s) of This m6A Regulator and Corresponding Disease/Drug Response(s)
ELF3 can regulate the m6A methylation of following target genes, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulted from the regulation of certain target gene.
Browse Target Gene related Disease
Androgen receptor (AR)
 Target Gene 
Prostate cancer [ICD-11: 2C82]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [1]
Responsed Disease Prostate cancer [ICD-11: 2C82]
In-vitro Model
 LNCaP Prostate carcinoma Homo sapiens CVCL_0395
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
In-vivo Model NOD.CB17-Prkdcscid/J none castrated SCID male mice 4 weeks old were purchased from Jackson Laboratories. After a one week period of acclimation, the mice were injected with 6×106 TetOn-Flag-ELF3 LNCaP suspended in 200 uL of a 50% mixture containing RPMI 1640 medium and Matrigel matrix basement membrane (BD Corporation, Bedford, MA) subcutaneously into the right flank region. The mice were either fed with doxycycline 200 mg/kg containing diet (BioServ, NJ) to induce the ELF3 expression or with a control regular diet. The sizes of the resultant tumors were measured weekly.
Response Summary ELF3 is a member of the ETS family of transcription factors, is a repressor of Androgen receptor (AR) transcriptional activity. Modulation of ELF3 expression and/or AR/ELF3 interaction has utility in the treatment of PC.
Mothers against decapentaplegic homolog 3 (SMAD3)
 Target Gene 
Chronic kidney disease [ICD-11: GB61]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [2]
Responsed Disease Chronic kidney disease [ICD-11: GB61.Z]
Pathway Response TGF-beta signaling pathway hsa04350
In-vitro Model
 Murine podocytes Normal Mus musculus CVCL_5737
In-vivo Model In the present study, we assessed Smad3 +/- mice for a comparatively long period to examine the effects of Smad3 expression and phosphorylation and to evaluate the involvement of Smad3 in DN. Heterozygous Smad3- knockout mice were kindly provided by Dr. Yasue, University of Tokushima. We attempted to generate Smad3-null mice using pairs of Smad3 mice, but progeny was rarely obtained, and pups were fragile and could not survive for a long period (5 weeks at the most). Therefore, BKS/Cg-m Lepr db (db/db) x Smad3 +/- mice were developed using pairs of Lepr db +/- x Smad3 +/-. Smad3 +/-;db/+ mice were generated by crossing Smad3 +/- and db/+ mice. Moreover, Smad3 +/-;db/db were generated by crossing Smad3 +/-;db/+ and db/+ mice as previously described. Blood glucose concentrations were measured from the tail vein (glucose assay kit; Abbott). The diabetic phenotype was confirmed 4 weeks after birth by blood glucose >300 mg/dl.
Response Summary Elf3 plays an important role in the process of phenotypic alterations of podocyte induced by the activation of TGF-beta signals. Elf3 protein levels in patients with DN (R2 = 0.7259) were useful as an early non-invasive marker for podocyte injuries in DN. The epithelium-specific transcription factor, Elf3 was induced by AGE stimulation and, subsequently, upregulated RII expression in cultured podocytes. Induction of Elf3 and activation of RII-Mothers against decapentaplegic homolog 3 (SMAD3) signaling, leading to a decrease in WT1 expression, were observed in podocytes in diabetic human kidneys.
Wilms tumor protein (WT1)
 Target Gene 
Chronic kidney disease [ICD-11: GB61]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [2]
Responsed Disease Chronic kidney disease [ICD-11: GB61.Z]
Pathway Response TGF-beta signaling pathway hsa04350
In-vitro Model
 Murine podocytes Normal Mus musculus CVCL_5737
Response Summary Elf3 plays an important role in the process of phenotypic alterations of podocyte induced by the activation of TGF-beta signals. Elf3 protein levels in patients with DN (R2 = 0.7259) were useful as an early non-invasive marker for podocyte injuries in DN. The epithelium-specific transcription factor, Elf3 was induced by AGE stimulation and, subsequently, upregulated RII expression in cultured podocytes. Induction of Elf3 and activation of RII-Smad3 signaling, leading to a decrease in Wilms tumor protein (WT1) expression, were observed in podocytes in diabetic human kidneys.
Click to View Potential Drug Response of This Regulator
Xenobiotics Compound(s) Regulating the m6A Methylation Regulator
Compound Name Rentinolol Investigative
Synonyms
CHEMBL2170196; Rentinolol; Wrenchnolol; SCHEMBL14003415; BDBM50396057
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External link
CID: 11228149
Activity
IC50=6900 nM
 [3]
References
Ref 1 ELF3 is a repressor of androgen receptor action in prostate cancer cells. Oncogene. 2014 Feb 13;33(7):862-71. doi: 10.1038/onc.2013.15. Epub 2013 Feb 25.
Ref 2 Involvement of Elf3 on Smad3 activation-dependent injuries in podocytes and excretion of urinary exosome in diabetic nephropathy. PLoS One. 2019 May 31;14(5):e0216788. doi: 10.1371/journal.pone.0216788. eCollection 2019.
Ref 3 ELF3 activated by a superenhancer and an autoregulatory feedback loop is required for high-level HLA-C expression on extravillous trophoblasts. Proc Natl Acad Sci U S A. 2021 Mar 2;118(9):e2025512118. doi: 10.1073/pnas.2025512118.