Identification and Functional Characterization of a Conserved, Nuclear Factor 1-like Element in the Proximal Promoter Region ofCYP1A2 Gene Specifically Expressed in the Liver and Olfactory Mucosa

CYP1A2 is a major cytochrome P-450 isoform in the liver and the olfactory mucosa but is essentially not expressed in other tissues. A nuclear factor 1 (NF-1) -like element was identified in the proximal promoter region of rat, mouse, rabbit, and humanCYP1A2 genes through data base analysis. In vitro DNase I footprinting with a −211 to +81 probe from the ratCYP1A2 gene and nuclear extracts from rat liver and olfactory mucosa revealed a single protected region corresponding to the NF-1-like element at −129 to −111. Protein binding to this NF-1-like element was tissue-selective and was confirmed by in vivo footprinting in native chromatin from rat liver. Multiple DNA-binding complexes were detected in gel-shift assays using theCYP1A2 NF-1-like element and nuclear extracts from liver and olfactory mucosa, all of which were supershifted in the presence of an anti-NF1 antibody. The NF-1-like element was essential for transcriptional activity of the CYP1A2 gene in an in vitro transcription assay using nuclear extracts from the two tissues. Thus, members of the NF-1 family of transcription factors may play an important role in the tissue-selective expression of theCYP1A2 gene in the liver and olfactory mucosa. CYP1A2 is a major cytochrome P-450 isoform in the liver and the olfactory mucosa but is essentially not expressed in other tissues. A nuclear factor 1 (NF-1) -like element was identified in the proximal promoter region of rat, mouse, rabbit, and humanCYP1A2 genes through data base analysis. In vitro DNase I footprinting with a −211 to +81 probe from the ratCYP1A2 gene and nuclear extracts from rat liver and olfactory mucosa revealed a single protected region corresponding to the NF-1-like element at −129 to −111. Protein binding to this NF-1-like element was tissue-selective and was confirmed by in vivo footprinting in native chromatin from rat liver. Multiple DNA-binding complexes were detected in gel-shift assays using theCYP1A2 NF-1-like element and nuclear extracts from liver and olfactory mucosa, all of which were supershifted in the presence of an anti-NF1 antibody. The NF-1-like element was essential for transcriptional activity of the CYP1A2 gene in an in vitro transcription assay using nuclear extracts from the two tissues. Thus, members of the NF-1 family of transcription factors may play an important role in the tissue-selective expression of theCYP1A2 gene in the liver and olfactory mucosa. cytochrome P-450 aryl hydrocarbon receptor base pair nuclear factor 1 nasal-predominant transcriptional activating polymerase chain reaction transthyretin CCAAT-binding transcription factor Tissue-selective gene expression, which is a common feature for most mammalian members of theCYP 1 gene superfamily, leads to important organ-selective functions and plays a critical role in tissue-selective toxicity of drugs and other xenobiotic compounds. Each tissue expresses a subset of xenobiotic-metabolizing P450 genes which determines, to a large extent, sensitivity of that organ to the toxicity of a given chemical compound. Variation in the levels of expression of P450 genes is one of the major contributing factors in interindividual and interspecies differences in susceptibility to environmental toxicants. Changes in P450 expression may result from alterations in those regulatory mechanisms, such as the transcriptional regulatory elements and the protein factors, which are potential targets for genetic polymorphism and cytotoxic events. However, despite recent progress in our understanding of xenobiotic-induced CYP gene expression, very limited advance has been made in identifying the elements and factors involved in the constitutive tissue- or cell-type-selective expression of xenobiotic-metabolizing P450s. CYP1A2 is constitutively expressed preferentially in the liver (1.Quattrochi L.C. Tukey R.H. Mol. Pharmacol. 1989; 36: 66-71PubMed Google Scholar) and the olfactory mucosa (2.Ding X. Coon M.J. Schenkman J.B. Greim H. Cytochrome P450: Handbook of Experimental Pharmacology. Springer-Verlag, New York1993: 351-361Google Scholar, 3.Genter M.B. Liang H.C. Gu J. Ding X. Negishi M. Mckinnon R.A. Nebert D.W. Biochem. Pharmacol. 1998; 55: 1819-1826Crossref PubMed Scopus (53) Google Scholar) in mammals. In the liver, CYP1A2is inducible by a number of xenobiotic compounds through AhR-mediated pathways (4.Tukey R.H. Nebert D.W. Biochemistry. 1984; 23: 6003-6008Crossref PubMed Scopus (55) Google Scholar, 5.Kimura S. Gonzalez F.J. Nebert D.W. Mol. Cell. Biol. 1986; 6: 1471-1477Crossref PubMed Scopus (173) Google Scholar, 6.Quattrochi L.C. Vu T. Tukey R.H. J. Biol. Chem. 1994; 269: 6949-6954Abstract Full Text PDF PubMed Google Scholar, 7.Fernandez-Salguero P. Pineau T. Hilbert D.M. McPhail T. Lee S.S. Kimura S. Nebert D.W. Rudikoff S. Ward J.M. Gonzalez F.J. Science. 1995; 268: 722-726Crossref PubMed Scopus (948) Google Scholar, 8.Schmidt J.V. Su G.H. Reddy J.K. Simon M.C. Bradfield C.A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 6731-6736Crossref PubMed Scopus (754) Google Scholar) as well as by other mechanisms (9.Pasco D.S. Boyum K.W. Merchant S.N. Chalberg S.C. Fagan J.B. J. Biol. Chem. 1988; 263: 8671-8676Abstract Full Text PDF PubMed Google Scholar, 10.Ryu D.Y. Levi P.E. Fernandez-Salguero P. Gonzalez F.J. Hodgson E. Mol. Pharmacol. 1996; 50: 443-446PubMed Google Scholar, 11.Corcos L. Marc N. Wein S. Fautrel A. Guillouzo A. Pineau T. FEBS Lett. 1998; 425: 293-297Crossref PubMed Scopus (32) Google Scholar, 12.Quattrochi L.C. Shih H. Pickwell G.V. Arch. Biochem. Biophys. 1998; 350: 41-48Crossref PubMed Scopus (23) Google Scholar), but significant induction of CYP1A2 has not been found in the olfactory mucosa (13.Gillner M. Brittebo E.B. Brandt I. Soderkvist P. Appelgren L.E. Gustafsson J.A. Cancer Res. 1987; 47: 4150-4159PubMed Google Scholar, 14.Ding X. Peng H.M. Pernecky S.J. Davis C.J. Coon M.J. Drug Metab. Dispos. 1992; 20: 792-796PubMed Google Scholar, 15.Wardlaw S.A. Nikula K.J. Kracko D.A. Finch G.L. Thornton-Manning J.R. Dahl A.R. Carcinogenesis. 1998; 19: 655-662Crossref PubMed Scopus (43) Google Scholar). CYP1A2 metabolizes several endogenous substances such as retinoids (16.Roberts E.S. Vaz A.D. Coon M.J. Mol. Pharmacol. 1992; 41: 427-433PubMed Google Scholar), arachidonic acid (17.Laethem R.M. Laethem C.L. Ding X. Koop D.R. J. Pharmacol. Exp. Ther. 1992; 262: 433-438PubMed Google Scholar), and the sex steroids (18.Waxman D.J. Attisano C. Guengerich F.P. Lapenson D.P. Arch. Biochem. Biophys. 1988; 262: 424-436Crossref Scopus (428) Google Scholar, 19.Aoyama T. Korzekwa J. Gonzalez F.J. PubMed Scopus Google Scholar) as well as xenobiotic environmental and such as and 1995; PubMed Scopus Google Scholar). gene expression may by as well as transcription factors Science. 1989; PubMed Scopus Google Scholar). the expression of P450 genes in the that P450 gene may by regulatory mechanisms F.J. Lee J. 1996; PubMed Scopus Google Scholar). is of the mechanisms involved in constitutive expression of the found that a pair to was for constitutive expression of a gene in R.A. Nebert D.W. Biochem. Biophys. Res. PubMed Scopus Google Scholar). However, a recent L.C. Vu T. Tukey R.H. J. Biol. Chem. 1994; 269: 6949-6954Abstract Full Text PDF PubMed Google Scholar) identified two in the of the CYP1A2 gene that were for induction by in to the and the other to which was to as an L.C. Shih H. Pickwell G.V. Arch. Biochem. Biophys. 1998; 350: 41-48Crossref PubMed Scopus (23) Google Scholar), an as well as two and a In a I. E. Mol. Pharmacol. 1995; 47: Google Scholar), a proximal to and a to of the CYP1A2 gene were found to important for the constitutive expression of a gene in The an and a for the liver transcription factor I. E. Arch. Biochem. Biophys. PubMed Scopus Google Scholar). The proximal and but protein binding to potential was not I. E. Mol. Pharmacol. 1995; 47: Google Scholar). recent with the that of the gene to constitutive expression of CYP1A2 in liver P. Pineau T. Hilbert D.M. McPhail T. Lee S.S. Kimura S. Nebert D.W. Rudikoff S. Ward J.M. Gonzalez F.J. Science. 1995; 268: 722-726Crossref PubMed Scopus (948) Google Scholar, 8.Schmidt J.V. Su G.H. Reddy J.K. Simon M.C. Bradfield C.A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 6731-6736Crossref PubMed Scopus (754) Google Scholar), is not the of constitutive CYP1A2 expression the from or mechanisms and is to the liver. identified a NF-1-like binding the involved in transcriptional and tissue-selective expression of rat and genes in the olfactory mucosa J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). The element with detected in the olfactory mucosa. a of gene revealed that an NF-1-like was in the proximal promoter region of rat, mouse, rabbit, and CYP1A2 CYP1A2 is expressed in the olfactory mucosa, in to the liver, the was to this NF-1-like is important for transcriptional and tissue-selective Thus, the proximal promoter region of rat CYP1A2 gene was using a number of to binding of nuclear to this NF-1-like and transcriptional olfactory and to this NF-1-like in the CYP1A2 gene were with the olfactory to the two genes common regulatory were from liver of essentially as J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar, M. U. Cell. 1986; 47: Full Text PDF PubMed Scopus Google Scholar, J. Biochemistry. PubMed Scopus Google Scholar) with were and in of for 1 The were with a in of an and and of a 1 and 1 and in of the in a for with and with A. The were through two of with tissue of in the to a of in and at for at in a The nuclear was in of a DNase I 1 and and at for in an The were in the DNase I at and with DNase I for The reaction was by with of a DNase I and 1 at for The were with A at for 1 and with an of The was with not in theCYP1A2 proximal promoter to by and as in as was essentially as by and Science. 1989; PubMed Scopus Google Scholar), with A of to the rat CYP1A2 gene were for the with the and as Science. 1989; PubMed Scopus Google Scholar). with 1 and from DNase with and the and reaction were all with of polymerase The were and the were by through a as J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). was by Science. 1989; PubMed Scopus Google Scholar) of rat liver that been with and to and PubMed Scopus Google Scholar). DNase I sensitivity of a of the in of a and 1 was with of DNase I at for The reaction was by with an of a and The was by to for in vitro transcription been J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar), as from and Gonzalez T. Gonzalez F.J. Mol. Cell. Biol. PubMed Scopus Google Scholar) and T. 1996; Scopus Google Scholar). as in in vitro transcription assays were in was by a to of the ratCYP1A2 gene at the of the this was by using rat as a and to the T. J. Biol. Chem. Full Text PDF PubMed Google Scholar). was made by of to a and to an using the The was as for promoter J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar), with of two one the of in CYP1A2 promoter and the other a in the in the A J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar), was in with olfactory mucosa, and a by a pair promoter C. R.H. J. J. PubMed Scopus Google Scholar), was in with liver. The was by from and the to the was as a from a from H. of the of at The of all promoter were by The for and in assays were to to of the CYP1A2 to of the and to of the The of the protected detected in assays were from the of the as J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). were by the of the for the and of for gel-shift and for assays been J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). for DNase I footprinting were by with one or and one of the with the as a were from at the from were for the of and nuclear extracts as J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). and assays were as J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). of a or a N. Cell. 1989; Full Text PDF PubMed Scopus Google Scholar) by of New was at with the nuclear extracts from liver or olfactory mucosa for 1 the of the probe In vitro DNase I footprinting were with the from as J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). were by the of the using an from Protein in nuclear extracts was using with as a The of were the of in the the of for footprinting were from the using of as of rat CYP1A2 promoter and been T. J. Biol. Chem. Full Text PDF PubMed Google Scholar). A single NF-1-like at −129 to was found by the data base T. E. I. H. Res. 1998; PubMed Scopus Google Scholar) using the with the at were found in the proximal promoter region of at to F.J. Kimura S. Nebert D.W. J. Biol. Chem. Full Text PDF PubMed Google Scholar), at to H. Tukey R.H. Arch. Biochem. Biophys. 1992; PubMed Scopus (32) Google Scholar), and at −129 to R.A. Nebert D.W. Kimura S. Mol. 1989; PubMed Scopus Google Scholar). In all the NF-1-like element is at of a However, the NF-1-like element is not in the CYP1A2 proximal promoter by (1.Quattrochi L.C. Tukey R.H. Mol. Pharmacol. 1989; 36: 66-71PubMed Google Scholar), as a result of a single of humanCYP1A2 proximal promoter region with from and not the at the NF-1-like element not that is A of the element with the element in the gene revealed significant at critical for binding J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). The presence of a NF-1 in the proximal promoter region of rat, mouse, and CYP1A2 genes potential in gene the genes are all to expressed tissue and in the liver and olfactory mucosa. this NF-1-like element with DNA-binding in vitro DNase I footprinting was using a −211 to +81 probe from the rat CYP1A2 gene with nuclear extracts from rat tissues. in a DNase I to was identified the with nuclear extracts from rat liver and olfactory mucosa, but not with those from and However, a of the was with extracts from the were with a probe the with the protected region at −129 to The of protein binding to this was confirmed by using an to to which the protected and two other and which in the critical for NF-1 R.M. Res. 1987; PubMed Scopus Google Scholar, R.M. S. R.A. J. Mol. Cell. Biol. PubMed Scopus Google Scholar) and binding J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). in and the was was at but was or not by the of and of nuclear to the NF-1-like element in the ratCYP1A2 gene was confirmed by in vivo DNase I footprinting The of the proximal promoter region T. J. Biol. Chem. Full Text PDF PubMed Google Scholar) and the of the for are in C. In to a single protected region to detected in in vitro several were revealed by in vivo footprinting the in the native chromatin of rat liver, as with the DNase I of rat The were with DNase I The most to the NF-1-like but the those detected by in vitro were detected and of the NF-1-like one to corresponding to a PubMed Scopus Google Scholar) and a one to to or M. Mol. Cell. Biol. PubMed Scopus Google Scholar). binding for the factor J. Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar) and the protein A. N. PubMed Scopus Google Scholar) are in this as in but corresponding were not in vivo were detected in rat olfactory mucosa or not most of the in and the of the The tissue-selective expression of nuclear to theCYP1A2 NF-1-like binding was in gel-shift with nuclear extracts from rat liver, olfactory mucosa, and in with the complexes were detected with nuclear extracts from liver and olfactory mucosa but not in the other were with which the major detected in liver and olfactory mucosa. are with the from DNase I assays and with CYP1A2 expressed in liver and olfactory mucosa but not the other tissues. Multiple were detected with nuclear extracts from liver and olfactory mucosa, but were differences in the the two 1 and the most with olfactory which the of all was in the liver. The other differences in the two tissues. was by of binding of liver and olfactory nuclear extracts by probe but not by two and or not that liver and olfactory nuclear with the NF-1-like element in rat CYP1A2 gene may potential and to the were with and and nuclear extracts from liver and olfactory mucosa. probe protein binding to in liver or olfactory nuclear extracts at an and protein binding to probe in olfactory nuclear extracts at a a of binding to the probe was at a of an of to the binding to probe However, as J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar) and confirmed in liver not to the the of olfactory complexes with the two and was that the major with probe those with the probe is and despite the the two to in the olfactory mucosa. The detected in gel-shift assays in that the CYP1A2 NF-1-like element may transcription factors, or through with an NF-1 which of the complexes an NF-1 assays were with a N. Cell. 1989; Full Text PDF PubMed Scopus Google Scholar), which has been in a number of to J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). and olfactory mucosa nuclear extracts were to the to with in the of to the reaction in the of a as well as a well in nuclear which was by in the of all detected in liver or olfactory mucosa. result is in to with the probe that of the the of the but not the most detected in olfactory nuclear extracts J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). The supershifted were not detected a was that all of the complexes with liver or olfactory nuclear extracts an NF-1 factor and that the were from binding with NF-1 factors or or with complexes of an NF-1 factor with other of In in the olfactory mucosa, the major to the element of the gene are from the the NF-1-like element plays a role in transcriptional of the CYP1A2 gene in the liver and the olfactory mucosa, in vitro transcription assays were The promoter in in are in A. from the CYP1A2 gene was detected by assay using a probe corresponding to the of the CYP1A2 A the as in which the binding activity of the probe in gel-shift assays was to the of the that to this NF-1-like were with J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar) and which were as for transcription in olfactory mucosa and liver, promoter been to of and expression of J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar) and C. R.H. J. J. PubMed Scopus Google Scholar) CYP1A2 were in with promoter using nuclear extracts from liver and or olfactory mucosa and but were with and In the transcription from the were the in the with or the transcription in olfactory nuclear transcription from the to from theCYP1A2 which was with the binding of and in the gel-shift assays and However, of at with not an of the transcription activity from the CYP1A2 and despite the in gel-shift assays with of which is in with the that with two that the NF-1-like element is for the transcriptional of the CYP1A2 gene in the olfactory mucosa and the liver and that the two at and are critical for protein binding and were made in this vitro footprinting and that protein binding to a NF-1-like element in the CYP1A2 gene was tissue-selective and with tissue-selective expression in liver and olfactory mucosa. this was essential for transcriptional of the CYP1A2 gene in vitro and was by DNA-binding in native from that all of the DNA-binding complexes with theCYP1A2 NF-1-like element NF-1 data that members of the NF-1 family of transcription factors may play an important role in the tissue-selective expression of the CYP1A2 gene in the liver and olfactory mucosa. A number of NF-1 transcription factors been which are from a family of at and J.R. C.A. Proc. Natl. Acad. Sci. U. S. A. 1988; PubMed Scopus Google Scholar, R.M. PubMed Scopus Google Scholar). NF-1 factors organ and expression and in transcriptional or J.R. C.A. Proc. Natl. Acad. Sci. U. S. A. 1988; PubMed Scopus Google Scholar, C. N. 1988; PubMed Scopus Google Scholar, Biochem. 1989; PubMed Scopus Google Scholar, J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). NF-1-like elements the been found in the and of an NF-1 is in the in and rat genes and is important for the of the induction P. Negishi M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, I. H. Biol. 1998; PubMed Scopus Google Scholar, C. A. Biochem. Pharmacol. PubMed Scopus Google Scholar). NF-1 element was found to a of the promoter in a with K.W. Mol. Cell. Biol. PubMed Scopus Google a is in rat and promoter and was found to involved in the of expression by J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). identified an NF-1-like regulatory element in the proximal promoter region of rat gene J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar), which may important for the tissue-selective expression of the gene in the olfactory mucosa. The element of the gene and the NF-1-like element of the CYP1A2 gene for protein binding in gel-shift with the CYP1A2 NF-1-like element a in liver and the olfactory mucosa. However, the element not nuclear in liver and the and olfactory to theCYP1A2 NF-1-like element were in from the olfactory is with the that not all complexes were supershifted by the in the J. Ding X. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). Thus, NF-1 factors may involved in the of genes to the expression of the gene and the but expression of the CYP1A2 gene in the liver and the olfactory mucosa. Multiple NF-1 been detected in the liver and the olfactory mucosa J. 1988; PubMed Scopus (173) Google Scholar, H. R.M. Mol. Res. PubMed Scopus Google Scholar). The in this was a protein the a and is to with the of and The of this with of the other NF-1 genes has not been that may A.D. D.M. J. Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar), an isoform from rat liver J. 1988; PubMed Scopus (173) Google Scholar), but may not in a rat J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). the of the and olfactory nuclear factors to the CYP1A2 NF-1-like element in vitro and in vivo are a was detected at the binding by in vivo in that a may in has been found that NF-1 factors with and with other factors N. Cell. 1989; Full Text PDF PubMed Scopus Google Scholar). were detected in the of the NF-1-like by the in vivo which that transcription factors may been or the of nuclear extracts for the in vitro footprinting or that the vitro were not for protein binding to The CYP1A2 NF-1-like element was protected by nuclear in in vitro footprinting However, gel-shift that the DNA-binding from rat were from those of the liver or olfactory mucosa. A recent that CYP1A2 was detected in tissue P. J. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar), and CYP1A2 was detected in induction by A. Nebert D.W. Biochem. Pharmacol. PubMed Scopus Google Scholar). However, the very of the complexes detected in rat nuclear extracts and the very levels of CYP1A2 expression to the role of the NF-1 factors in the of CYP1A2 expression in the The CYP1A2 NF-1-like element is in and in which the tissue-selective expression of CYP1A2 in the liver and olfactory mucosa has been In CYP1A2 is one of the major P450 in the liver, but expression in olfactory mucosa has not been of the CYP1A2 gene been by two (1.Quattrochi L.C. Tukey R.H. Mol. Pharmacol. 1989; 36: 66-71PubMed Google R.A. Nebert D.W. Kimura S. Mol. 1989; PubMed Scopus Google at a critical in the NF-1-like element in this of (1.Quattrochi L.C. Tukey R.H. Mol. Pharmacol. 1989; 36: 66-71PubMed Google Scholar) a single that the the two which the element However, of detected the corresponding to the NF-1-like element but not that of the Thus, this NF-1-like element is in to confirmed and a that a genetic polymorphism at this in a large interindividual in been 1995; PubMed Scopus Google Scholar). polymorphism of the humanCYP1A2 gene was not found G.H. Drug Metab. Dispos. Google Scholar, M. T. M. M. M. T. J. Biochem. PubMed Scopus Google Scholar, C. J. S. I. J. Pharmacol. 47: PubMed Scopus Google Scholar, M. PubMed Scopus Google Scholar), and a single at was found to significant M. T. M. M. M. T. J. Biochem. PubMed Scopus Google Scholar). was to a factor of CYP1A2 in The of the constitutive expression of the humanCYP1A2 gene has been in a in I. E. Mol. Pharmacol. 1995; 47: Google Scholar). of and not a in gene expression, but of to gene was that this to a a and a is essential for constitutive expression of the CYP1A2 regulatory elements may for promoter this result to in to the with the rat that the NF-1-like element at −129 to is important for the promoter the of the proximal promoter region of the CYP1A2 in that I. E. Mol. Pharmacol. 1995; 47: Google Scholar) was not is not the NF-1-like element at −129 to −111. the expresses CYP1A2 at a by I. E. Arch. Biochem. Biophys. 1994; PubMed Scopus Google Scholar). Thus, critical transcriptional may not or may expressed at levels to the endogenous or as I. E. Mol. Pharmacol. 1995; 47: Google Scholar). the other the may differences and the the to found in the humanCYP1A2 gene is not found at in rat, mouse, or CYP1A2 genes T. J. Biol. Chem. Full Text PDF PubMed Google Scholar, F.J. Kimura S. Nebert D.W. J. Biol. Chem. Full Text PDF PubMed Google Scholar, H. Tukey R.H. Arch. Biochem. Biophys. 1992; PubMed Scopus (32) Google Scholar). The expression of CYP1A2 in that this transcription factor may or involved in the constitutive expression of the CYP1A2 gene P. Pineau T. Hilbert D.M. McPhail T. Lee S.S. Kimura S. Nebert D.W. Rudikoff S. Ward J.M. Gonzalez F.J. Science. 1995; 268: 722-726Crossref PubMed Scopus (948) Google Scholar, 8.Schmidt J.V. Su G.H. Reddy J.K. Simon M.C. Bradfield C.A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 6731-6736Crossref PubMed Scopus (754) Google Scholar). of with a of not the or the of the or olfactory complexes with the CYP1A2 NF-1-like and X. that the factors are not by the AhR-mediated Thus, the are in the region of the CYP1A2 gene L.C. Vu T. Tukey R.H. J. Biol. Chem. 1994; 269: 6949-6954Abstract Full Text PDF PubMed Google Scholar), from the NF-1-like constitutive expression of CYP1A2 may the two regulatory a has been in the of expression by N. Mol. Cell. Biol. 19: PubMed Google Scholar). H. of the of at for the of New for the and for the the of the of the

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