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Alternative promoter usage is typically associated with mRNAs with differing first exons that contain or consist entirely of a 5' untranslated region. The murine Bcrp1 (Abcg2) transporter has three alternative promoters associated with mRNAs containing alternative untranslated first exons designated as E1A, E1B, and E1C. The E1B promoter regulates Bcrp1 transcription in mouse intestine. Here, we report the identification and characterization of a novel Bcrp1 promoter and first exon, E1U, located upstream from the other Bcrp1 promoters/first exons, which is the predominant alternative promoter utilized in murine testis. Using in silico analysis we identified a putative steroidogenic factor-1 (SF-1) response element that was unique to the Bcrp1 E1U alternative promoter. Overexpression of SF-1 in murine TM4 Sertoli cells enhanced Bcrp1 E1U mRNA expression and increased Bcrp1 E1U alternative promoter activity in a reporter assay, whereas mutation of the SF-1 binding site totally eliminated Bcrp1 E1U alternative promoter activity. Moreover, expression of Bcrp1 E1U and total mRNA and Bcrp1 protein was markedly diminished in the testes from adult Sertoli cell-specific SF-1 knockout mice, in comparison to the testes from wild-type mice. Binding of SF-1 to the SF-1 response element in the E1U promoter was demonstrated by chromatin immunoprecipitation assays. In conclusion, nuclear transcription factor SF-1 is involved with the regulation of a novel promoter of Bcrp1 that governs transcription of the E1U mRNA isoform in mice. The present study furthers understanding of the complex regulation of Bcrp1 expression in specific tissues of a mammalian model.

Titel:	Bcrp1 transcription in mouse testis is controlled by a promoter upstream of a novel first exon (E1U) regulated by steroidogenic factor-1.
Autor/in / Beteiligte Person:	Xie, Y ; Natarajan, K ; Bauer, KS ; Nakanishi, T ; Beck, WT ; Moreci, RS ; Jeyasuria, P ; Hussain, A ; Ross, DD
Zeitschrift:	Biochimica et biophysica acta, Jg. 1829 (2013-12-01), Heft 12, S. 1288-99
Veröffentlichung:	Amsterdam : Elsevier Pub. Co., 2013
Medientyp:	academicJournal
ISSN:	0006-3002 (print)
DOI:	10.1016/j.bbagrm.2013.10.008
Schlagwort:	5' Untranslated Regions ATP Binding Cassette Transporter, Subfamily G, Member 2 ATP-Binding Cassette Transporters metabolism Animals Blotting, Western Cells, Cultured Chromatin Immunoprecipitation Luciferases metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Mutation genetics Organ Specificity RNA Splicing Factors RNA, Messenger genetics Real-Time Polymerase Chain Reaction Response Elements genetics Reverse Transcriptase Polymerase Chain Reaction Sertoli Cells cytology Transcription, Genetic genetics Transfection ATP-Binding Cassette Transporters genetics DNA-Binding Proteins physiology Exons genetics Gene Expression Regulation Promoter Regions, Genetic genetics Sertoli Cells metabolism Testis metabolism Transcription Factors physiology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Language: English [Biochim Biophys Acta] 2013 Dec; Vol. 1829 (12), pp. 1288-99. <i>Date of Electronic Publication: </i>2013 Nov 02. MeSH Terms: Gene Expression Regulation* ; ATP-Binding Cassette Transporters / genetics ; DNA-Binding Proteins / physiology ; Exons / genetics ; Promoter Regions, Genetic / genetics ; Sertoli Cells / metabolism ; Testis / metabolism ; Transcription Factors / *physiology ; 5' Untranslated Regions ; ATP Binding Cassette Transporter, Subfamily G, Member 2 ; ATP-Binding Cassette Transporters / metabolism ; Animals ; Blotting, Western ; Cells, Cultured ; Chromatin Immunoprecipitation ; Luciferases / metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mutation / genetics ; Organ Specificity ; RNA Splicing Factors ; RNA, Messenger / genetics ; Real-Time Polymerase Chain Reaction ; Response Elements / genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sertoli Cells / cytology ; Transcription, Genetic / genetics ; Transfection References: Bioinformatics. 2002 Jan;18(1):198-9. (PMID: 11836231) ; Mol Pharmacol. 2010 Aug;78(2):175-85. (PMID: 20460431) ; J Biol Chem. 2005 Jun 3;280(22):21491-7. (PMID: 15790569) ; Mol Cell Endocrinol. 2011 Apr 10;336(1-2):198-205. (PMID: 21078366) ; Mol Endocrinol. 2001 Jan;15(1):80-92. (PMID: 11145741) ; Cell Tissue Res. 2012 Aug;349(2):551-63. (PMID: 22581381) ; J Biol Chem. 2001 Oct 5;276(40):37659-64. (PMID: 11479297) ; Mol Cell Biol. 2005 Dec;25(23):10442-53. (PMID: 16287857) ; Leuk Res. 2011 Oct;35(10):1321-9. (PMID: 21640380) ; J Biol Chem. 1998 May 29;273(22):13391-4. (PMID: 9593668) ; Pharmacogenetics. 1999 Apr;9(2):145-53. (PMID: 10376761) ; J Mol Biol. 1995 Jun 23;249(5):923-32. (PMID: 7791218) ; Biofizika. 2006 Jul-Aug;51(4):633-9. (PMID: 16909840) ; Methods Enzymol. 2003;370:237-50. (PMID: 14712649) ; Asian J Androl. 2013 Jul;15(4):455-60. (PMID: 23665760) ; Drug Metab Dispos. 2005 Apr;33(4):524-9. (PMID: 15640379) ; Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15665-70. (PMID: 9861027) ; Cancer Res. 2001 Apr 15;61(8):3458-64. (PMID: 11309308) ; Drug Metab Dispos. 2008 Jun;36(6):995-1002. (PMID: 18322075) ; Nat Med. 2005 Feb;11(2):127-9. (PMID: 15685169) ; Nucleic Acids Res. 2002 Jan 1;30(1):312-7. (PMID: 11752324) ; Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10338-42. (PMID: 19506252) ; Endocrinology. 2004 May;145(5):2186-96. (PMID: 14736734) ; Mol Cell Endocrinol. 2013 May 22;371(1-2):154-9. (PMID: 23168267) ; J Mol Graph Model. 2003 Mar;21(5):323-32. (PMID: 12543131) ; J Biol Chem. 2006 Oct 6;281(40):29625-32. (PMID: 16885162) ; Nucleic Acids Res. 2003 Jul 1;31(13):3554-9. (PMID: 12824364) ; Mol Endocrinol. 2004 Jul;18(7):1610-9. (PMID: 15118069) ; Neuroreport. 2002 Nov 15;13(16):2059-63. (PMID: 12438926) ; J Natl Cancer Inst. 2000 Oct 18;92(20):1651-6. (PMID: 11036110) ; Cytogenet Genome Res. 2003;101(3-4):242-9. (PMID: 14684990) ; Biochem Pharmacol. 2012 Apr 15;83(8):1084-103. (PMID: 22248732) ; J Pharmacol Exp Ther. 2010 Jun;333(3):788-96. (PMID: 20304939) ; Biochem Biophys Res Commun. 2005 Jan 7;326(1):181-7. (PMID: 15567169) ; Cancer Res. 2006 May 15;66(10):5007-11. (PMID: 16707421) ; Recent Prog Horm Res. 2002;57:129-48. (PMID: 12017540) ; Biochim Biophys Acta. 2011 Jul;1809(7):295-305. (PMID: 21718815) ; Biol Reprod. 1980 Aug;23(1):243-52. (PMID: 6774781) ; Development. 2001 Jan;128(2):147-54. (PMID: 11124111) ; J Pharmacol Exp Ther. 2012 Jan;340(1):96-108. (PMID: 21990609) ; Development. 2004 Jan;131(2):479-87. (PMID: 14681185) ; Genesis. 2002 Jul;33(3):114-8. (PMID: 12124943) ; J Neurosci. 2009 Apr 29;29(17):5463-75. (PMID: 19403814) ; Kidney Int. 2008 Jan;73(2):220-5. (PMID: 17978814) ; Biochem Biophys Res Commun. 2009 Jan 9;378(2):302-7. (PMID: 19032939) ; Nucleic Acids Res. 2003 Jul 1;31(13):3540-5. (PMID: 12824362) ; Arterioscler Thromb Vasc Biol. 2008 Jun;28(6):1097-103. (PMID: 18356551) ; Eur J Cancer. 2004 Sep;40(14):2064-70. (PMID: 15341980) ; Cancer Lett. 2006 Apr 8;235(1):84-92. (PMID: 15990223) Grant Information: R01 CA040570 United States CA NCI NIH HHS; CA40570 United States CA NCI NIH HHS Contributed Indexing: Keywords: 5′ UTR; 5′ untranslated region; Breast cancer resistance protein (ABCG2); Mouse; Promoter; SF-1; Steroidogenic factor-1 (SF-1); TSS; Testis; steroidogenic factor-1; transcriptional start site Substance Nomenclature: 0 (5' Untranslated Regions) ; 0 (ATP Binding Cassette Transporter, Subfamily G, Member 2) ; 0 (ATP-Binding Cassette Transporters) ; 0 (Abcg2 protein, mouse) ; 0 (DNA-Binding Proteins) ; 0 (RNA Splicing Factors) ; 0 (RNA, Messenger) ; 0 (Sf1 protein, mouse) ; 0 (Transcription Factors) ; EC 1.13.12.- (Luciferases) Entry Date(s): Date Created: 20131106 Date Completed: 20140211 Latest Revision: 20211021 Update Code: 20231215 PubMed Central ID: PMC3873745

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Bcrp1 transcription in mouse testis is controlled by a promoter upstream of a novel first exon (E1U) regulated by steroidogenic factor-1.