| Structural highlights
Function
[ELF3_MOUSE] 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 (By similarity). Also transactivates collagenase, CCL20, CLND7, FLG, KRT8, NOS2, PTGS2, SPRR2B, TGFBR2 and TGM3 promoters. Represses KRT4 promoter activity (By similarity). 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 (By similarity). 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.[1] [2] [3] [4] [5] [6] [7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The Ets family of transcription factors is composed of more than 30 members. One of its members, Elf3, is expressed in virtually all epithelial cells as well as in many tumors, including breast tumors. Several studies observed that the promoter of the type II TGF-beta receptor gene (TbetaR-II) is strongly stimulated by Elf3 via two adjacent Elf3 binding sites, the A-site and the B-site. Here, we report the 2.2 A resolution crystal structure of a mouse Elf3 C-terminal fragment, containing the DNA-binding Ets domain, in complex with the B-site of mouse type II TGF-beta receptor promoter DNA (mTbetaR-II(DNA)). Elf3 contacts the core GGAA motif of the B-site from a major groove similar to that of known Ets proteins. However, unlike other Ets proteins, Elf3 also contacts sequences of the A-site from the minor groove of the DNA. DNA binding experiments and cell-based transcription studies indicate that minor groove interaction by Arg349 located in the Ets domain is important for Elf3 function. Equally interesting, previous studies have shown that the C-terminal region of Elf3, which flanks the Ets domain, is required for Elf3 binding to DNA. In this study, we determined that Elf3 amino acid residues within this flanking region, including Trp361, are important for the structural integrity of the protein as well as for the Efl3 DNA binding and transactivation activity.
Crystal structure of mouse Elf3 C-terminal DNA-binding domain in complex with type II TGF-beta receptor promoter DNA.,Agarkar VB, Babayeva ND, Wilder PJ, Rizzino A, Tahirov TH J Mol Biol. 2010 Mar 19;397(1):278-89. Epub 2010 Jan 15. PMID:20079749[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Neve R, Chang CH, Scott GK, Wong A, Friis RR, Hynes NE, Benz CC. The epithelium-specific ets transcription factor ESX is associated with mammary gland development and involution. FASEB J. 1998 Nov;12(14):1541-50. PMID:9806763
- ↑ Ng AY, Waring P, Ristevski S, Wang C, Wilson T, Pritchard M, Hertzog P, Kola I. Inactivation of the transcription factor Elf3 in mice results in dysmorphogenesis and altered differentiation of intestinal epithelium. Gastroenterology. 2002 May;122(5):1455-66. PMID:11984530
- ↑ Kim JH, Wilder PJ, Hou J, Nowling T, Rizzino A. Activation of the murine type II transforming growth factor-beta receptor gene: up-regulation and function of the transcription factor Elf-3/Ert/Esx/Ese-1. J Biol Chem. 2002 May 17;277(20):17520-30. Epub 2002 Mar 13. PMID:11893733 doi:10.1074/jbc.M110434200
- ↑ Kageyama S, Liu H, Nagata M, Aoki F. The role of ETS transcription factors in transcription and development of mouse preimplantation embryos. Biochem Biophys Res Commun. 2006 Jun 2;344(2):675-9. Epub 2006 Apr 17. PMID:16630543 doi:10.1016/j.bbrc.2006.03.192
- ↑ Tymms MJ, Ng AY, Thomas RS, Schutte BC, Zhou J, Eyre HJ, Sutherland GR, Seth A, Rosenberg M, Papas T, Debouck C, Kola I. A novel epithelial-expressed ETS gene, ELF3: human and murine cDNA sequences, murine genomic organization, human mapping to 1q32.2 and expression in tissues and cancer. Oncogene. 1997 Nov 13;15(20):2449-62. PMID:9395241 doi:10.1038/sj.onc.1201427
- ↑ Yoshida N, Yoshida S, Araie M, Handa H, Nabeshima Y. Ets family transcription factor ESE-1 is expressed in corneal epithelial cells and is involved in their differentiation. Mech Dev. 2000 Oct;97(1-2):27-34. PMID:11025204
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- ↑ Agarkar VB, Babayeva ND, Wilder PJ, Rizzino A, Tahirov TH. Crystal structure of mouse Elf3 C-terminal DNA-binding domain in complex with type II TGF-beta receptor promoter DNA. J Mol Biol. 2010 Mar 19;397(1):278-89. Epub 2010 Jan 15. PMID:20079749 doi:10.1016/j.jmb.2010.01.017
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