FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2017695170> ?p ?o ?g. }

• W2017695170 endingPage "22129" @default.
• W2017695170 startingPage "22125" @default.
• W2017695170 abstract "The CYP11A1 gene encodes the cholesterol side-chain cleavage enzyme P450scc, which catalyzes the synthesis of steroids from cholesterol. This gene is expressed only in steroidogenic organs such as the adrenal, gonad, placenta, and brain. We have characterized an upstream regulatory element of the human CYP11A1 gene, termed AdE, which contributed to its cell type-specific expression. The AdE sequence contains two protein binding regions, AdE1 and AdE2, which bind many proteins including NF1- and Sp1-like proteins as shown by electrophoretic mobility shift assay, footprinting, competition, antibody supershift, and mutagenesis of the binding sites. When cloned in front of the CYP11A1 promoter or the heterologous thymidine kinase promoter, AdE sequences enhanced expression of the reporter gene in steroidogenic cell lines of the adrenal, gonad, and placental origin but not in nonsteroidogenic cell lines such as COS-1 and Rat-1. The function of AdE1 and AdE2 was lower when present individually than together. The combined action of multiple transcription factors binding to the AdE sequence brings about the final activation of the CYP11A1 gene in a tissue-specific manner. The CYP11A1 gene encodes the cholesterol side-chain cleavage enzyme P450scc, which catalyzes the synthesis of steroids from cholesterol. This gene is expressed only in steroidogenic organs such as the adrenal, gonad, placenta, and brain. We have characterized an upstream regulatory element of the human CYP11A1 gene, termed AdE, which contributed to its cell type-specific expression. The AdE sequence contains two protein binding regions, AdE1 and AdE2, which bind many proteins including NF1- and Sp1-like proteins as shown by electrophoretic mobility shift assay, footprinting, competition, antibody supershift, and mutagenesis of the binding sites. When cloned in front of the CYP11A1 promoter or the heterologous thymidine kinase promoter, AdE sequences enhanced expression of the reporter gene in steroidogenic cell lines of the adrenal, gonad, and placental origin but not in nonsteroidogenic cell lines such as COS-1 and Rat-1. The function of AdE1 and AdE2 was lower when present individually than together. The combined action of multiple transcription factors binding to the AdE sequence brings about the final activation of the CYP11A1 gene in a tissue-specific manner. INTRODUCTIONThe CYP11A1 (SCC) gene encodes the enzyme cytochrome P450scc (cholesterol side-chain cleavage enzyme) that catalyzes the conversion of cholesterol to pregnenolone, the first and rate-limiting step in the synthesis of all steroids (1Miller W.L. Endocr. Rev. 1988; 9: 295-318Crossref PubMed Scopus (1169) Google Scholar). P450scc functions as a monooxygenase in the mitochondrion, using electrons transported from its cofactor ferredoxin reductase and ferredoxin for oxidation/reduction reactions. The human SCC gene is located on chromosome 15 (2Chung B.-C. Matteson K.J. Voutilainen R. Mohandas T.K. Miller W.L. Proc. Natl. Acad. Sci. U. S. A. 1986; 83: 8962-8966Crossref PubMed Scopus (316) Google Scholar). Its expression follows a developmentally programmed, cell type-specific, and hormonally regulated pattern. P450scc first appears in the adrenal primordia and fetal gonads at gestational days 11-12 in rodent embryos (3Rogler L.E. Pintar J.E. Mol. Endocrinol. 1993; 7: 453-461PubMed Google Scholar, 4Ikeda Y. Shen W.-H. Ingraham H.A. Parker K.L. Mol. Endocrinol. 1994; 8: 654-662Crossref PubMed Scopus (540) Google Scholar). The expression of P450scc is further stimulated by adrenocorticotropin and gonadotropin in the adrenal and gonads, respectively, using cAMP as an intracellular mediator (5Simpson E.R. Waterman M.R. Annu. Rev. Physiol. 1988; 50: 427-440Crossref PubMed Scopus (421) Google Scholar). In addition, there are other sites of P450scc expression. Placenta expresses P450scc to provide progesterone necessary for pregnancy (2Chung B.-C. Matteson K.J. Voutilainen R. Mohandas T.K. Miller W.L. Proc. Natl. Acad. Sci. U. S. A. 1986; 83: 8962-8966Crossref PubMed Scopus (316) Google Scholar). Brain and the primitive gut of mouse embryo express a small amount of P450scc (6Keeney D.S. Ikeda Y. Waterman M.R. Parker K.L. Mol. Endocrinol. 1995; 9: 1091-1098PubMed Google Scholar, 7Mellon S.H. Deschepper C.F. Brain Res. 1993; 629: 283-292Crossref PubMed Scopus (354) Google Scholar). With a few exceptions (8Chen C.-T. Guo I.-C. Chung B.-C. DNA Cell Biol. 1995; 9: 803-810Crossref Scopus (18) Google Scholar), regulation of P450scc gene expression in most cell types is at the transcriptional level (9John M.E. John M.C. Boggaram V. Simpson E.R. Waterman M.R. Proc. Natl. Acad. Sci. U. S. A. 1986; 83: 4715-4719Crossref PubMed Scopus (209) Google Scholar).The cis-acting elements that control the tissue-specific and hormonal regulation of the SCC gene have been under extensive investigation (10Waterman M.R. J. Biol. Chem. 1994; 269: 27783-27786Abstract Full Text PDF PubMed Google Scholar). Sites responsible for cAMP-dependent expression have been identified. One site close to the basal promoter consists of G-rich sequences which bind Sp1-like proteins (11Guo I.-C. Tsai H.-M. Chung B. J. Biol. Chem. 1994; 269: 6362-6369Abstract Full Text PDF PubMed Google Scholar, 12Venepally P. Waterman M.R. J. Biol. Chem. 1995; 270: 25402-25410Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar). This G-rich sequence is also found in other steroidogenic genes such as ferredoxin (13Chang C.-Y. Huang C. Guo I.-C. Tsai H.-M. Wu D.-A. Chung B.-C. Mol. Endocrinol. 1992; 6: 1362-1370PubMed Google Scholar), CYP21 (14Chang S.-F. Chung B.-C. Mol. Endocrinol. 1995; 9: 1330-1336Crossref PubMed Google Scholar), and CYP19 (15Zhao Y. Mendelson C.R. Simpson E.R. Mol. Endocrinol. 1995; 9: 340-349Crossref PubMed Google Scholar). Another cAMP-responsive sequence is located further upstream and contain sequences similar to cAMP-responsive element termed CRE (16Watanabe N. Inoue H. Fujii-Kuriyama Y. Eur. J. Biochem. 1994; 222: 825-834Crossref PubMed Scopus (44) Google Scholar). The sequence controlling phorbol ester response was found close to the basal promoter of the SCC gene (17Moore C.C.D. Brentano S.T. Miller W.L. Mol. Cell Biol. 1990; 10: 6013-6023Crossref PubMed Scopus (119) Google Scholar, 18Lauber M.E. Picton H.M. Begeot M. Momoi K. Waterman M.R. Simpson E.R. Mol. Cell. Endocrinol. 1993; 94: 235-242Crossref PubMed Scopus (15) Google Scholar).In different cell types, the expression of the SCC gene follows different regulatory mechanisms. The adrenal and placenta use different control elements for gene expression and cAMP stimulation (19Guo I.-C. Huang C. Chung B.-C. DNA Cell Biol. 1993; 12: 849-860Crossref PubMed Scopus (34) Google Scholar, 20Hum D.W. Aza-Blanc P. Miller W.L. DNA Cell Biol. 1995; 14: 451-463Crossref PubMed Scopus (31) Google Scholar). Glioma cell line C6 also contains transcription factors that are different from those in the adrenal cell line Y1 for gene expression (21Zhang P. Rodriguez H. Mellon S.H. Mol. Endocrinol. 1995; 9: 1571-1582Crossref PubMed Google Scholar). The adrenal and gonads are derived from the same progenitor cells (4Ikeda Y. Shen W.-H. Ingraham H.A. Parker K.L. Mol. Endocrinol. 1994; 8: 654-662Crossref PubMed Scopus (540) Google Scholar); therefore it is not surprising that they share the same transcriptional control elements.One major transcription factor in the adrenal and gonad that controls SCC gene expression is steroidogenic factor 1 (SF1 or Ad4BP). 1The abbreviations used are: SF1steroidogenic factor 1oligooligonucleotidetkthymidine kinaseCATchloramphenicol acetyltransferase. SF1 is a member of the nuclear hormone receptor family that binds to the AAGGTCA sequence (22Honda S. Morohashi K. Nomura M. Takeya H. Omura T. J. Biol. Chem. 1993; 268: 7494-7502Abstract Full Text PDF PubMed Google Scholar). Almost all steroidogenic genes including SCC contains AAGGTCA sequence and is stimulated by SF1 transcriptionally (23Rice D.A. Mouw A.R. Bogerd A.M. Parker K.L. Mol. Endocrinol. 1991; 5: 1552-1561Crossref PubMed Scopus (220) Google Scholar). SF1, however, is not the only factor that controls tissue-specific expression of steroidogenic genes. P450c21 and P450c11 are expressed only in the adrenal, despite the abundant expression of SF1 in the gonad. Therefore, there must be other transcription factors that control the adrenal-specific expression of P450c21 and P450c11. The equal distribution of SF1 in all three zones of the adrenal cortex cannot explain zone-specific transcription of CYP11B1 (24Mukai K. Mitani F. Shimada H. Ishimura Y. Mol. Cell. Biol. 1995; 15: 6003-6012Crossref PubMed Scopus (32) Google Scholar). In addition, SF1 alone does not achieve the highest level of expression observed in these cell types.Previously we have identified a DNA region at 1.9 kilobase pairs upstream from the transcription start site that augments transcription of the human SCC promoter above the basal level (11Guo I.-C. Tsai H.-M. Chung B. J. Biol. Chem. 1994; 269: 6362-6369Abstract Full Text PDF PubMed Google Scholar). In this report we have further characterized this region and found that multiple proteins including Sp1- and NF1-like proteins bind to this region. The combined action of these proteins upon binding to the upstream sites resulted in cell type-specific enhancement of transcription of the human SCC gene.DISCUSSIONIn this report, we characterized the upstream AdE elements of the human CYP11A1 gene. The sequence was composed of two major protein binding regions AdE1 and AdE2, which functioned in steroidogenic cell-specific gene activation. All the tested steroidogenic cell lines, including two adrenal cell lines Y1 and H295, a mouse testis Leydig cell line MA10, and a human placental cell line JEG-3, support the activation function of AdE elements (Table II). The AdE sequences, on the other hand, are not functional in nonsteroidogenic cell lines COS-1 and Rat-1.Besides AdE, a key regulator for steroidogenic gene expression, transcription factor SF1, functions in many steroidogenic cells including adrenal and gonad (36Ikeda Y. Lala D.S. Luo X. Kim E. Moisan M.-R. Parker K.L. Mol. Endocrinol. 1993; 7: 852-860Crossref PubMed Google Scholar). SF1, however, is not expressed in such steroidogenic organ as placenta. 2I.-C. Guo and B.-C. Chung, unpublished observation. Therefore SF1 is not the sole factor that determines cell type specificity of steroidogenic gene expression. AdE sequences are functional in multiple steroidogenic cells including placenta, showing that they could enhance or modulate SCC transcription in many steroidogenic cells.Many proteins bound to the AdE sequences. NF1-like proteins were the most prominent ones. The rest included Sp1-like and other as yet unidentified proteins. NF1 belongs to a protein family containing related proteins which recognize similar TGG(C/A)(N)5GCCAA sequences (35Goyal N. Knox J. Gronostajski R.M. Mol. Cell. Biol. 1990; 10: 1041-1048Crossref PubMed Scopus (67) Google Scholar, 38Santoro C. Mermod N. Andrews P.C. Tjian R. Nature. 1988; 334: 218-224Crossref PubMed Scopus (491) Google Scholar, 39Gil G. Smith J.R. Goldstein J.L. Slaughter C.A. Orth K. Brown M.S. Osborne T.F. Proc. Natl. Acad. Sci. U. S. A. 1988; 85: 8963-8967Crossref PubMed Scopus (137) Google Scholar). NF1 family members function widely in replication and transcription of various viral and cellular genes (40Rossi P. Karsenty G. Roberts A.B. Roche N.S. Sporn M.B. de Crombrugghe B. Cell. 1988; 52: 405-414Abstract Full Text PDF PubMed Scopus (444) Google Scholar, 41Gounari F. de Francesco R. Schmitt J. van der Vliet P.C. Cortese R. Stunnenberg H. EMBO J. 1990; 9: 559-566Crossref PubMed Scopus (120) Google Scholar, 42Jones K.A. Kadonaga J.T. Rosenfeld P.J. Kelly T.J. Tjian R. Cell. 1987; 48: 79-89Abstract Full Text PDF PubMed Scopus (566) Google Scholar, 43Allan G.F. Ing N.H. Tsai S.Y. Srinivasan G. Weigel N.L. Thompson E.B. Tsai M.-J. O'Malley B.W. J. Biol. Chem. 1991; 266: 5905-5910Abstract Full Text PDF PubMed Google Scholar, 44Lichtsteiner S. Wuarin J. Schibler U. Cell. 1987; 51: 963-973Abstract Full Text PDF PubMed Scopus (300) Google Scholar, 45Eskild W. Simard J. Hansson V. Guárin S.L. Mol. Endocrinol. 1994; 8: 732-745PubMed Google Scholar, 46Courtois S.J. Lafontaine D.A. Lemaigre F.P. Durviaux S.M. Rousseau G.R. Nucleic Acids Res. 1990; 18: 57-64Crossref PubMed Scopus (76) Google Scholar, 47Hennighausen L. Furth P.A. Pittius C.W. Nucleic Acids Res. 1989; 17: 8197-8206Crossref PubMed Scopus (3) Google Scholar). Sp1, on the other hand, activates transcription of many genes through its binding to the GGGGCGG or GGGGAGG sequences (48Kadonaga J.T. Jones K.A. Tjian R. Trends Biochem. Sci. 1986; 11: 20-23Abstract Full Text PDF Scopus (875) Google Scholar). Sp1 also belongs to a protein family consisting of multiple related members with similar DNA-binding specificity (49Hagen G. Müller S. Beato M. Suske G. Nucleic Acids Res. 1992; 20: 5519-5525Crossref PubMed Scopus (522) Google Scholar, 50Kingsley C. Winoto A. Mol. Cell. Biol. 1992; 12: 4251-4261Crossref PubMed Scopus (487) Google Scholar, 51Hagen G. Müller S. Beato M. Suske G. EMBO J. 1994; 13: 3843-3851Crossref PubMed Scopus (650) Google Scholar).Both NF1 and Sp1 exert their activation function through interaction with other transcription factors. Sp1 has been shown to form multimeric complexes (52Pascal E. Tjian R. Genes & Dev. 1991; 5: 1646-1656Crossref PubMed Scopus (354) Google Scholar), to interact with coactivators (53Gill G. Pascal E. Tseng Z.H. Tjian R. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 192-196Crossref PubMed Scopus (469) Google Scholar) and other transcription factors (54Anderson G.M. Freytag S.O. Mol. Cell. Biol. 1991; 11: 1935-1943Crossref PubMed Scopus (84) Google Scholar, 55Weintraub S.J. Dean D.C. Mol. Cell. Biol. 1992; 12: 512-517Crossref PubMed Scopus (30) Google Scholar, 56Kamine J. Subramanian T. Chinnadurai G. Proc. Natl. Acad. Sci. U. S. A. 1991; 88: 8510-8514Crossref PubMed Scopus (107) Google Scholar, 57Li R. Knight J.D. Jackson S.P. Tjian R. Botchan M.R. Cell. 1991; 65: 493-505Abstract Full Text PDF PubMed Scopus (224) Google Scholar). Likewise, NF1 exerts its function through synergistic interaction with a number of different transcription factors in a wide range of situations (43Allan G.F. Ing N.H. Tsai S.Y. Srinivasan G. Weigel N.L. Thompson E.B. Tsai M.-J. O'Malley B.W. J. Biol. Chem. 1991; 266: 5905-5910Abstract Full Text PDF PubMed Google Scholar, 44Lichtsteiner S. Wuarin J. Schibler U. Cell. 1987; 51: 963-973Abstract Full Text PDF PubMed Scopus (300) Google Scholar, 47Hennighausen L. Furth P.A. Pittius C.W. Nucleic Acids Res. 1989; 17: 8197-8206Crossref PubMed Scopus (3) Google Scholar). Combinatorial interaction of various transcription factors bound to their cognate binding sites of the gene has become a paradigm of eukaryotic gene activation.NF1 and Sp1 are both considered general transcription factors. In deed, NF1- and Sp1-like proteins were also found bound to the AdE sequences in COS-1 cells (data not shown). It is therefore intriguing to find out how common transcription factors can determine cell type-specific expression. NF1 family members have been shown to be involved in liver-, adipocyte-, and epithelial cell-specific functions (58Jackson D.A. Rowader K.E. Stevens K. Jiang C. Milos P. Zaret K.S. Mol. Cell. Biol. 1993; 13: 2401-2410Crossref PubMed Scopus (134) Google Scholar, 59Graves R.A. Tontonoz P. Ross S.R. Spiegelman B.M. Genes & Dev. 1991; 5: 428-437Crossref PubMed Scopus (117) Google Scholar, 60Chong T. Apt D. Gloss B. Isa M. Bernard H.-U. J. Virol. 1991; 65: 5933-5943Crossref PubMed Google Scholar). It is believed that synergism between factors that vary in concentration in different cells results in cell type-specific transcriptional activation (61Grayson J. Williams R.S. Yu Y.-T. Bassel-Duby R. Mol. Cell. Biol. 1995; 15: 1870-1878Crossref PubMed Scopus (55) Google Scholar, 62Costa R.H. Grayson D.R. Darnell Jr., J.E. Mol. Cell. Biol. 1989; 9: 1415-1425Crossref PubMed Scopus (427) Google Scholar, 63Bouvagnet P.F. Strehler E.E. White G.E. Strehler-Page M.-A. Nadal-Ginard B. Mahdavi V. Mol. Cell. Biol. 1987; 7: 4377-4389Crossref PubMed Scopus (60) Google Scholar, 64Shieh S.-Y. Tsai M.-J. J. Biol. Chem. 1991; 266: 16708-16714Abstract Full Text PDF PubMed Google Scholar). In one situation, NF1 could interact with tissue-specific transcription factors for tissue-specific activation (58Jackson D.A. Rowader K.E. Stevens K. Jiang C. Milos P. Zaret K.S. Mol. Cell. Biol. 1993; 13: 2401-2410Crossref PubMed Scopus (134) Google Scholar, 65Graves R.A. Tontonoz P. Spiegelman B.M. Mol. Cell. Biol. 1992; 12: 1202-1208Crossref PubMed Scopus (84) Google Scholar). In the other situation, it is the balance of different NF1 family members that controls cell type specificity. In epithelial cells, the NF1 protein is derived from NF1-C, although in fibroblast cells, the major NF1 protein is NF1-X. NF1-X protein fails to activate enhancer function due to a variation in its activation domain. It is the property of NF1-X and the differential concentration of the NF1 family members that achieve the epithelial cell specificity of NF1 for human papillomavirus 16 expression (66Apt D. Liu Y. Bernard H. Nucleic Acids Res. 1994; 22: 3825-3833Crossref PubMed Scopus (76) Google Scholar).Although being viewed as a ubiquitous transcription factor, substantial variations in Sp1 expression were found in different cell types, showing that its expression is developmentally programmed (67Saffer J.D. Jackson S.P. Annarella M.B. Mol. Cell. Biol. 1991; 11: 2189-2199Crossref PubMed Scopus (483) Google Scholar). Because Sp1 belongs to a protein family consisting of multiple related members with similar DNA-binding specificity (49Hagen G. Müller S. Beato M. Suske G. Nucleic Acids Res. 1992; 20: 5519-5525Crossref PubMed Scopus (522) Google Scholar, 50Kingsley C. Winoto A. Mol. Cell. Biol. 1992; 12: 4251-4261Crossref PubMed Scopus (487) Google Scholar, 51Hagen G. Müller S. Beato M. Suske G. EMBO J. 1994; 13: 3843-3851Crossref PubMed Scopus (650) Google Scholar), it is possible that the variations in Sp1 levels in different cell types are attributed to detection of different members of the Sp1 family in these tissues. Some members of the Sp1 family could be expressed in a tissue-specific manner. BTEB2, an Sp1 family member that is homologous to Sp1 at the DNA-binding domain and recognizes the same GC box, is expressed specifically in testis and placenta (37Sogawa K. Imataka H. Yamasaki Y. Kusume H. Abe H. Fujii-Kuriyama Y. Nucleic Acids Res. 1993; 21: 1527-1532Crossref PubMed Scopus (179) Google Scholar). We showed that the Sp1-like protein being bound to the AdE sequences recognized the same sequence and shared the same antigenicity with Sp1, yet we do not know which member of the Sp1 family binds to the AdE sequences. It is possible that the tissue-specific expression of the SCC gene is determined by the steroidogenic tissue-specific expression of the BTEB-2-like protein.In conclusion, the AdE sequences of the human SCC gene contains binding sites for Sp1- and NF1-like proteins. It is the combined action of these bound and interacting factors that brings about the final activation of the SCC gene in a steroidogenic cell-specific manner. INTRODUCTIONThe CYP11A1 (SCC) gene encodes the enzyme cytochrome P450scc (cholesterol side-chain cleavage enzyme) that catalyzes the conversion of cholesterol to pregnenolone, the first and rate-limiting step in the synthesis of all steroids (1Miller W.L. Endocr. Rev. 1988; 9: 295-318Crossref PubMed Scopus (1169) Google Scholar). P450scc functions as a monooxygenase in the mitochondrion, using electrons transported from its cofactor ferredoxin reductase and ferredoxin for oxidation/reduction reactions. The human SCC gene is located on chromosome 15 (2Chung B.-C. Matteson K.J. Voutilainen R. Mohandas T.K. Miller W.L. Proc. Natl. Acad. Sci. U. S. A. 1986; 83: 8962-8966Crossref PubMed Scopus (316) Google Scholar). Its expression follows a developmentally programmed, cell type-specific, and hormonally regulated pattern. P450scc first appears in the adrenal primordia and fetal gonads at gestational days 11-12 in rodent embryos (3Rogler L.E. Pintar J.E. Mol. Endocrinol. 1993; 7: 453-461PubMed Google Scholar, 4Ikeda Y. Shen W.-H. Ingraham H.A. Parker K.L. Mol. Endocrinol. 1994; 8: 654-662Crossref PubMed Scopus (540) Google Scholar). The expression of P450scc is further stimulated by adrenocorticotropin and gonadotropin in the adrenal and gonads, respectively, using cAMP as an intracellular mediator (5Simpson E.R. Waterman M.R. Annu. Rev. Physiol. 1988; 50: 427-440Crossref PubMed Scopus (421) Google Scholar). In addition, there are other sites of P450scc expression. Placenta expresses P450scc to provide progesterone necessary for pregnancy (2Chung B.-C. Matteson K.J. Voutilainen R. Mohandas T.K. Miller W.L. Proc. Natl. Acad. Sci. U. S. A. 1986; 83: 8962-8966Crossref PubMed Scopus (316) Google Scholar). Brain and the primitive gut of mouse embryo express a small amount of P450scc (6Keeney D.S. Ikeda Y. Waterman M.R. Parker K.L. Mol. Endocrinol. 1995; 9: 1091-1098PubMed Google Scholar, 7Mellon S.H. Deschepper C.F. Brain Res. 1993; 629: 283-292Crossref PubMed Scopus (354) Google Scholar). With a few exceptions (8Chen C.-T. Guo I.-C. Chung B.-C. DNA Cell Biol. 1995; 9: 803-810Crossref Scopus (18) Google Scholar), regulation of P450scc gene expression in most cell types is at the transcriptional level (9John M.E. John M.C. Boggaram V. Simpson E.R. Waterman M.R. Proc. Natl. Acad. Sci. U. S. A. 1986; 83: 4715-4719Crossref PubMed Scopus (209) Google Scholar).The cis-acting elements that control the tissue-specific and hormonal regulation of the SCC gene have been under extensive investigation (10Waterman M.R. J. Biol. Chem. 1994; 269: 27783-27786Abstract Full Text PDF PubMed Google Scholar). Sites responsible for cAMP-dependent expression have been identified. One site close to the basal promoter consists of G-rich sequences which bind Sp1-like proteins (11Guo I.-C. Tsai H.-M. Chung B. J. Biol. Chem. 1994; 269: 6362-6369Abstract Full Text PDF PubMed Google Scholar, 12Venepally P. Waterman M.R. J. Biol. Chem. 1995; 270: 25402-25410Abstract Full Text Full Text PDF PubMed Scopus (83) Google Scholar). This G-rich sequence is also found in other steroidogenic genes such as ferredoxin (13Chang C.-Y. Huang C. Guo I.-C. Tsai H.-M. Wu D.-A. Chung B.-C. Mol. Endocrinol. 1992; 6: 1362-1370PubMed Google Scholar), CYP21 (14Chang S.-F. Chung B.-C. Mol. Endocrinol. 1995; 9: 1330-1336Crossref PubMed Google Scholar), and CYP19 (15Zhao Y. Mendelson C.R. Simpson E.R. Mol. Endocrinol. 1995; 9: 340-349Crossref PubMed Google Scholar). Another cAMP-responsive sequence is located further upstream and contain sequences similar to cAMP-responsive element termed CRE (16Watanabe N. Inoue H. Fujii-Kuriyama Y. Eur. J. Biochem. 1994; 222: 825-834Crossref PubMed Scopus (44) Google Scholar). The sequence controlling phorbol ester response was found close to the basal promoter of the SCC gene (17Moore C.C.D. Brentano S.T. Miller W.L. Mol. Cell Biol. 1990; 10: 6013-6023Crossref PubMed Scopus (119) Google Scholar, 18Lauber M.E. Picton H.M. Begeot M. Momoi K. Waterman M.R. Simpson E.R. Mol. Cell. Endocrinol. 1993; 94: 235-242Crossref PubMed Scopus (15) Google Scholar).In different cell types, the expression of the SCC gene follows different regulatory mechanisms. The adrenal and placenta use different control elements for gene expression and cAMP stimulation (19Guo I.-C. Huang C. Chung B.-C. DNA Cell Biol. 1993; 12: 849-860Crossref PubMed Scopus (34) Google Scholar, 20Hum D.W. Aza-Blanc P. Miller W.L. DNA Cell Biol. 1995; 14: 451-463Crossref PubMed Scopus (31) Google Scholar). Glioma cell line C6 also contains transcription factors that are different from those in the adrenal cell line Y1 for gene expression (21Zhang P. Rodriguez H. Mellon S.H. Mol. Endocrinol. 1995; 9: 1571-1582Crossref PubMed Google Scholar). The adrenal and gonads are derived from the same progenitor cells (4Ikeda Y. Shen W.-H. Ingraham H.A. Parker K.L. Mol. Endocrinol. 1994; 8: 654-662Crossref PubMed Scopus (540) Google Scholar); therefore it is not surprising that they share the same transcriptional control elements.One major transcription factor in the adrenal and gonad that controls SCC gene expression is steroidogenic factor 1 (SF1 or Ad4BP). 1The abbreviations used are: SF1steroidogenic factor 1oligooligonucleotidetkthymidine kinaseCATchloramphenicol acetyltransferase. SF1 is a member of the nuclear hormone receptor family that binds to the AAGGTCA sequence (22Honda S. Morohashi K. Nomura M. Takeya H. Omura T. J. Biol. Chem. 1993; 268: 7494-7502Abstract Full Text PDF PubMed Google Scholar). Almost all steroidogenic genes including SCC contains AAGGTCA sequence and is stimulated by SF1 transcriptionally (23Rice D.A. Mouw A.R. Bogerd A.M. Parker K.L. Mol. Endocrinol. 1991; 5: 1552-1561Crossref PubMed Scopus (220) Google Scholar). SF1, however, is not the only factor that controls tissue-specific expression of steroidogenic genes. P450c21 and P450c11 are expressed only in the adrenal, despite the abundant expression of SF1 in the gonad. Therefore, there must be other transcription factors that control the adrenal-specific expression of P450c21 and P450c11. The equal distribution of SF1 in all three zones of the adrenal cortex cannot explain zone-specific transcription of CYP11B1 (24Mukai K. Mitani F. Shimada H. Ishimura Y. Mol. Cell. Biol. 1995; 15: 6003-6012Crossref PubMed Scopus (32) Google Scholar). In addition, SF1 alone does not achieve the highest level of expression observed in these cell types.Previously we have identified a DNA region at 1.9 kilobase pairs upstream from the transcription start site that augments transcription of the human SCC promoter above the basal level (11Guo I.-C. Tsai H.-M. Chung B. J. Biol. Chem. 1994; 269: 6362-6369Abstract Full Text PDF PubMed Google Scholar). In this report we have further characterized this region and found that multiple proteins including Sp1- and NF1-like proteins bind to this region. The combined action of these proteins upon binding to the upstream sites resulted in cell type-specific enhancement of transcription of the human SCC gene." @default.
• W2017695170 created "2016-06-24" @default.
• W2017695170 creator A5063479813 @default.
• W2017695170 creator A5071977277 @default.
• W2017695170 creator A5076039054 @default.
• W2017695170 date "1996-09-01" @default.
• W2017695170 modified "2023-10-16" @default.
• W2017695170 title "Characterization of the Upstream Sequence of the Human CYP11A1 Gene for Cell Type-specific Expression" @default.
• W2017695170 cites W1031388349 @default.
• W2017695170 cites W1228798347 @default.
• W2017695170 cites W1519038850 @default.
• W2017695170 cites W1525127751 @default.
• W2017695170 cites W1528256607 @default.
• W2017695170 cites W1533192527 @default.
• W2017695170 cites W1595565542 @default.
• W2017695170 cites W1640150978 @default.
• W2017695170 cites W1750321095 @default.
• W2017695170 cites W1965705977 @default.
• W2017695170 cites W1968013290 @default.
• W2017695170 cites W1972890620 @default.
• W2017695170 cites W1981929643 @default.
• W2017695170 cites W1982558048 @default.
• W2017695170 cites W1983512144 @default.
• W2017695170 cites W1990563288 @default.
• W2017695170 cites W1992919675 @default.
• W2017695170 cites W1996075074 @default.
• W2017695170 cites W2003893812 @default.
• W2017695170 cites W2006362317 @default.
• W2017695170 cites W2014319693 @default.
• W2017695170 cites W2027152017 @default.
• W2017695170 cites W2028466678 @default.
• W2017695170 cites W2030621682 @default.
• W2017695170 cites W2041233862 @default.
• W2017695170 cites W2047058509 @default.
• W2017695170 cites W2059394258 @default.
• W2017695170 cites W2066156515 @default.
• W2017695170 cites W2072550491 @default.
• W2017695170 cites W2076134621 @default.
• W2017695170 cites W2081008299 @default.
• W2017695170 cites W2082685929 @default.
• W2017695170 cites W2086178662 @default.
• W2017695170 cites W2088167128 @default.
• W2017695170 cites W2101243954 @default.
• W2017695170 cites W2102122649 @default.
• W2017695170 cites W2106979182 @default.
• W2017695170 cites W2112157195 @default.
• W2017695170 cites W2125701765 @default.
• W2017695170 cites W2130258789 @default.
• W2017695170 cites W2130535740 @default.
• W2017695170 cites W2147452643 @default.
• W2017695170 cites W2162716015 @default.
• W2017695170 cites W2169653086 @default.
• W2017695170 cites W2240323633 @default.
• W2017695170 cites W4247756202 @default.
• W2017695170 cites W54669141 @default.
• W2017695170 doi "https://doi.org/10.1074/jbc.271.36.22125" @default.
• W2017695170 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/8703023" @default.
• W2017695170 hasPublicationYear "1996" @default.
• W2017695170 type Work @default.
• W2017695170 sameAs 2017695170 @default.
• W2017695170 citedByCount "29" @default.
• W2017695170 countsByYear W20176951702013 @default.
• W2017695170 countsByYear W20176951702016 @default.
• W2017695170 crossrefType "journal-article" @default.
• W2017695170 hasAuthorship W2017695170A5063479813 @default.
• W2017695170 hasAuthorship W2017695170A5071977277 @default.
• W2017695170 hasAuthorship W2017695170A5076039054 @default.
• W2017695170 hasConcept C104317684 @default.
• W2017695170 hasConcept C105580179 @default.
• W2017695170 hasConcept C150194340 @default.
• W2017695170 hasConcept C191172861 @default.
• W2017695170 hasConcept C2778112365 @default.
• W2017695170 hasConcept C41008148 @default.
• W2017695170 hasConcept C54355233 @default.
• W2017695170 hasConcept C70721500 @default.
• W2017695170 hasConcept C76155785 @default.
• W2017695170 hasConcept C80446465 @default.
• W2017695170 hasConcept C86803240 @default.
• W2017695170 hasConceptScore W2017695170C104317684 @default.
• W2017695170 hasConceptScore W2017695170C105580179 @default.
• W2017695170 hasConceptScore W2017695170C150194340 @default.
• W2017695170 hasConceptScore W2017695170C191172861 @default.
• W2017695170 hasConceptScore W2017695170C2778112365 @default.
• W2017695170 hasConceptScore W2017695170C41008148 @default.
• W2017695170 hasConceptScore W2017695170C54355233 @default.
• W2017695170 hasConceptScore W2017695170C70721500 @default.
• W2017695170 hasConceptScore W2017695170C76155785 @default.
• W2017695170 hasConceptScore W2017695170C80446465 @default.
• W2017695170 hasConceptScore W2017695170C86803240 @default.
• W2017695170 hasIssue "36" @default.
• W2017695170 hasLocation W20176951701 @default.
• W2017695170 hasOpenAccess W2017695170 @default.
• W2017695170 hasPrimaryLocation W20176951701 @default.
• W2017695170 hasRelatedWork W1991523530 @default.
• W2017695170 hasRelatedWork W2002128513 @default.
• W2017695170 hasRelatedWork W2009966535 @default.
• W2017695170 hasRelatedWork W2020824267 @default.
• W2017695170 hasRelatedWork W2031436818 @default.

• next