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The human CYP1A2 gene and induction by 3-methylcholanthrene. A region of DNA that supports AH-receptor binding and promoter-specific induction
The gene for cytochrome P4501A2 is constitutively expressed in the liver of vertebrates and shows induced expression when an organism is exposed to polycyclic aromatic hydrocarbons and halogenated hydrocarbons. To identify DNA elements regulating transcription of the human CYP1A2 gene, transient tra...
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| Published in: | The Journal of biological chemistry 1994-03, Vol.269 (9), p.6949-6954 |
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| creator | Quattrochi, L C Vu, T Tukey, R H |
| description | The gene for cytochrome P4501A2 is constitutively expressed in the liver of vertebrates and shows induced expression when
an organism is exposed to polycyclic aromatic hydrocarbons and halogenated hydrocarbons. To identify DNA elements regulating
transcription of the human CYP1A2 gene, transient transfection experiments were conducted in the human hepatoma cell line
HepG2. Dissection of the 5'-flanking portion of the CYP1A2 gene identified two regions that contributed to the overall induction
by 3-methylcholanthrene. One region located at -2532/-2423 contains an xenobiotic-responsive element-like sequence, termed
X1, that binds a nuclear 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible protein in HepG2 and wild type mouse Hepa-1 cells,
but not in the Ah receptor nuclear translocation defective mouse C- mutant c4 cells. In addition, deletion of this region
of the CYP1A2 gene reduces the 3-methylcholanthrene (3-MC)-initiated induction of chloramphenicol acetyltransferase activity
in both promoter- and enhancer-specific constructs. The second responsive region is located at -2259/-1987. This region of
the gene contains a second xenobiotic-responsive element-like element, but this element does not associate with the nuclear
Ah receptor. However, there does exist several potential AP1 binding sites and a conserved TATA box. A DNA fragment from -2259/-1970
that contains these elements was shown to function as an efficient eukaryotic promoter, in addition to supporting 3-MC-induced
promoter activity. These results suggest that Ah receptor-specific and promoter-specific elements regulate the expression
of the human CYP1A2 gene. |
| doi_str_mv | 10.1016/S0021-9258(17)37466-5 |
| format | article |
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an organism is exposed to polycyclic aromatic hydrocarbons and halogenated hydrocarbons. To identify DNA elements regulating
transcription of the human CYP1A2 gene, transient transfection experiments were conducted in the human hepatoma cell line
HepG2. Dissection of the 5'-flanking portion of the CYP1A2 gene identified two regions that contributed to the overall induction
by 3-methylcholanthrene. One region located at -2532/-2423 contains an xenobiotic-responsive element-like sequence, termed
X1, that binds a nuclear 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible protein in HepG2 and wild type mouse Hepa-1 cells,
but not in the Ah receptor nuclear translocation defective mouse C- mutant c4 cells. In addition, deletion of this region
of the CYP1A2 gene reduces the 3-methylcholanthrene (3-MC)-initiated induction of chloramphenicol acetyltransferase activity
in both promoter- and enhancer-specific constructs. The second responsive region is located at -2259/-1987. This region of
the gene contains a second xenobiotic-responsive element-like element, but this element does not associate with the nuclear
Ah receptor. However, there does exist several potential AP1 binding sites and a conserved TATA box. A DNA fragment from -2259/-1970
that contains these elements was shown to function as an efficient eukaryotic promoter, in addition to supporting 3-MC-induced
promoter activity. These results suggest that Ah receptor-specific and promoter-specific elements regulate the expression
of the human CYP1A2 gene.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1016/S0021-9258(17)37466-5</identifier><identifier>PMID: 8120057</identifier><identifier>CODEN: JBCHA3</identifier><language>eng</language><publisher>Bethesda, MD: American Society for Biochemistry and Molecular Biology</publisher><subject>Animals ; Base Sequence ; Binding Sites ; Biological and medical sciences ; Carcinoma, Hepatocellular ; Cell Line ; Cell Nucleus - metabolism ; Cytochrome P-450 CYP1A2 ; Cytochrome P-450 Enzyme System - biosynthesis ; Cytochrome P-450 Enzyme System - genetics ; DNA - metabolism ; DNA-Binding Proteins - metabolism ; Enzyme Induction ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation - drug effects ; Hominidae - genetics ; Humans ; Liver Neoplasms ; Methylcholanthrene - pharmacology ; Mice ; Molecular and cellular biology ; Molecular genetics ; Molecular Sequence Data ; Nuclear Proteins - isolation & purification ; Nuclear Proteins - metabolism ; Oligonucleotide Probes ; Oxidoreductases, N-Demethylating - biosynthesis ; Oxidoreductases, N-Demethylating - genetics ; Polychlorinated Dibenzodioxins - pharmacology ; Promoter Regions, Genetic ; Receptors, Aryl Hydrocarbon - metabolism ; Sequence Deletion ; Sequence Homology, Nucleic Acid ; Transcription. Transcription factor. Splicing. Rna processing ; Transfection ; Tumor Cells, Cultured</subject><ispartof>The Journal of biological chemistry, 1994-03, Vol.269 (9), p.6949-6954</ispartof><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-1255d33db1da299f13d6176f2055f1dfbcde49ed1f4d714a64b3c28b4e0199f73</citedby><cites>FETCH-LOGICAL-c438t-1255d33db1da299f13d6176f2055f1dfbcde49ed1f4d714a64b3c28b4e0199f73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,783,787,27936,27937</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4073251$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8120057$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Quattrochi, L C</creatorcontrib><creatorcontrib>Vu, T</creatorcontrib><creatorcontrib>Tukey, R H</creatorcontrib><title>The human CYP1A2 gene and induction by 3-methylcholanthrene. A region of DNA that supports AH-receptor binding and promoter-specific induction</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>The gene for cytochrome P4501A2 is constitutively expressed in the liver of vertebrates and shows induced expression when
an organism is exposed to polycyclic aromatic hydrocarbons and halogenated hydrocarbons. To identify DNA elements regulating
transcription of the human CYP1A2 gene, transient transfection experiments were conducted in the human hepatoma cell line
HepG2. Dissection of the 5'-flanking portion of the CYP1A2 gene identified two regions that contributed to the overall induction
by 3-methylcholanthrene. One region located at -2532/-2423 contains an xenobiotic-responsive element-like sequence, termed
X1, that binds a nuclear 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible protein in HepG2 and wild type mouse Hepa-1 cells,
but not in the Ah receptor nuclear translocation defective mouse C- mutant c4 cells. In addition, deletion of this region
of the CYP1A2 gene reduces the 3-methylcholanthrene (3-MC)-initiated induction of chloramphenicol acetyltransferase activity
in both promoter- and enhancer-specific constructs. The second responsive region is located at -2259/-1987. This region of
the gene contains a second xenobiotic-responsive element-like element, but this element does not associate with the nuclear
Ah receptor. However, there does exist several potential AP1 binding sites and a conserved TATA box. A DNA fragment from -2259/-1970
that contains these elements was shown to function as an efficient eukaryotic promoter, in addition to supporting 3-MC-induced
promoter activity. These results suggest that Ah receptor-specific and promoter-specific elements regulate the expression
of the human CYP1A2 gene.</description><subject>Animals</subject><subject>Base Sequence</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Hepatocellular</subject><subject>Cell Line</subject><subject>Cell Nucleus - metabolism</subject><subject>Cytochrome P-450 CYP1A2</subject><subject>Cytochrome P-450 Enzyme System - biosynthesis</subject><subject>Cytochrome P-450 Enzyme System - genetics</subject><subject>DNA - metabolism</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Enzyme Induction</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Hominidae - genetics</subject><subject>Humans</subject><subject>Liver Neoplasms</subject><subject>Methylcholanthrene - pharmacology</subject><subject>Mice</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Molecular Sequence Data</subject><subject>Nuclear Proteins - isolation & purification</subject><subject>Nuclear Proteins - metabolism</subject><subject>Oligonucleotide Probes</subject><subject>Oxidoreductases, N-Demethylating - biosynthesis</subject><subject>Oxidoreductases, N-Demethylating - genetics</subject><subject>Polychlorinated Dibenzodioxins - pharmacology</subject><subject>Promoter Regions, Genetic</subject><subject>Receptors, Aryl Hydrocarbon - metabolism</subject><subject>Sequence Deletion</subject><subject>Sequence Homology, Nucleic Acid</subject><subject>Transcription. Transcription factor. Splicing. Rna processing</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><recordid>eNpFkV2L1DAUhoMo6-zqT1gIIqIXXXOSJm0uy-i6wqKCK-hVSJN0Gpk23SRF5k_4m-18MJ6bc3Ge856PF6FrIDdAQLz_TgiFQlJev4XqHatKIQr-BK2A1KxgHH4-Rasz8hxdpvSbLFFKuEAXNVBCeLVCfx96h_t50CNe__oGDcUbNzqsR4v9aGeTfRhxu8OsGFzud1vTh60ecx8X6gY3OLrNnggd_vClwbnXGad5mkLMCTd3RXTGTTlE3C5qftwchKcYhpBdLNLkjO-8-T_qBXrW6W1yL0_5Cv24_fiwvivuv376vG7uC1OyOhdAObeM2RasplJ2wKyASnSUcN6B7VpjXSmdha60FZRalC0ztG5LR2DBK3aF3hx1l10eZ5eyGnwybrvc5sKcFIhaCMnYAvIjaGJIKbpOTdEPOu4UELX3QR18UPsnK6jUwQfFl77r04C5HZw9d50ev9Rfn-o6Gb3toh6NT2esJBWjHBbs1RHr_ab_46NTrQ-md4OiQiqphCwl-wfL45x4</recordid><startdate>19940304</startdate><enddate>19940304</enddate><creator>Quattrochi, L C</creator><creator>Vu, T</creator><creator>Tukey, R H</creator><general>American Society for Biochemistry and Molecular Biology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope></search><sort><creationdate>19940304</creationdate><title>The human CYP1A2 gene and induction by 3-methylcholanthrene. A region of DNA that supports AH-receptor binding and promoter-specific induction</title><author>Quattrochi, L C ; Vu, T ; Tukey, R H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-1255d33db1da299f13d6176f2055f1dfbcde49ed1f4d714a64b3c28b4e0199f73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Animals</topic><topic>Base Sequence</topic><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Hepatocellular</topic><topic>Cell Line</topic><topic>Cell Nucleus - metabolism</topic><topic>Cytochrome P-450 CYP1A2</topic><topic>Cytochrome P-450 Enzyme System - biosynthesis</topic><topic>Cytochrome P-450 Enzyme System - genetics</topic><topic>DNA - metabolism</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Enzyme Induction</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Hominidae - genetics</topic><topic>Humans</topic><topic>Liver Neoplasms</topic><topic>Methylcholanthrene - pharmacology</topic><topic>Mice</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Molecular Sequence Data</topic><topic>Nuclear Proteins - isolation & purification</topic><topic>Nuclear Proteins - metabolism</topic><topic>Oligonucleotide Probes</topic><topic>Oxidoreductases, N-Demethylating - biosynthesis</topic><topic>Oxidoreductases, N-Demethylating - genetics</topic><topic>Polychlorinated Dibenzodioxins - pharmacology</topic><topic>Promoter Regions, Genetic</topic><topic>Receptors, Aryl Hydrocarbon - metabolism</topic><topic>Sequence Deletion</topic><topic>Sequence Homology, Nucleic Acid</topic><topic>Transcription. Transcription factor. Splicing. Rna processing</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Quattrochi, L C</creatorcontrib><creatorcontrib>Vu, T</creatorcontrib><creatorcontrib>Tukey, R H</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Quattrochi, L C</au><au>Vu, T</au><au>Tukey, R H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The human CYP1A2 gene and induction by 3-methylcholanthrene. A region of DNA that supports AH-receptor binding and promoter-specific induction</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1994-03-04</date><risdate>1994</risdate><volume>269</volume><issue>9</issue><spage>6949</spage><epage>6954</epage><pages>6949-6954</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><coden>JBCHA3</coden><abstract>The gene for cytochrome P4501A2 is constitutively expressed in the liver of vertebrates and shows induced expression when
an organism is exposed to polycyclic aromatic hydrocarbons and halogenated hydrocarbons. To identify DNA elements regulating
transcription of the human CYP1A2 gene, transient transfection experiments were conducted in the human hepatoma cell line
HepG2. Dissection of the 5'-flanking portion of the CYP1A2 gene identified two regions that contributed to the overall induction
by 3-methylcholanthrene. One region located at -2532/-2423 contains an xenobiotic-responsive element-like sequence, termed
X1, that binds a nuclear 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible protein in HepG2 and wild type mouse Hepa-1 cells,
but not in the Ah receptor nuclear translocation defective mouse C- mutant c4 cells. In addition, deletion of this region
of the CYP1A2 gene reduces the 3-methylcholanthrene (3-MC)-initiated induction of chloramphenicol acetyltransferase activity
in both promoter- and enhancer-specific constructs. The second responsive region is located at -2259/-1987. This region of
the gene contains a second xenobiotic-responsive element-like element, but this element does not associate with the nuclear
Ah receptor. However, there does exist several potential AP1 binding sites and a conserved TATA box. A DNA fragment from -2259/-1970
that contains these elements was shown to function as an efficient eukaryotic promoter, in addition to supporting 3-MC-induced
promoter activity. These results suggest that Ah receptor-specific and promoter-specific elements regulate the expression
of the human CYP1A2 gene.</abstract><cop>Bethesda, MD</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>8120057</pmid><doi>10.1016/S0021-9258(17)37466-5</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of biological chemistry, 1994-03, Vol.269 (9), p.6949-6954 |
| issn | 0021-9258 1083-351X |
| language | eng |
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| source | ScienceDirect Journals |
| subjects | Animals Base Sequence Binding Sites Biological and medical sciences Carcinoma, Hepatocellular Cell Line Cell Nucleus - metabolism Cytochrome P-450 CYP1A2 Cytochrome P-450 Enzyme System - biosynthesis Cytochrome P-450 Enzyme System - genetics DNA - metabolism DNA-Binding Proteins - metabolism Enzyme Induction Fundamental and applied biological sciences. Psychology Gene Expression Regulation - drug effects Hominidae - genetics Humans Liver Neoplasms Methylcholanthrene - pharmacology Mice Molecular and cellular biology Molecular genetics Molecular Sequence Data Nuclear Proteins - isolation & purification Nuclear Proteins - metabolism Oligonucleotide Probes Oxidoreductases, N-Demethylating - biosynthesis Oxidoreductases, N-Demethylating - genetics Polychlorinated Dibenzodioxins - pharmacology Promoter Regions, Genetic Receptors, Aryl Hydrocarbon - metabolism Sequence Deletion Sequence Homology, Nucleic Acid Transcription. Transcription factor. Splicing. Rna processing Transfection Tumor Cells, Cultured |
| title | The human CYP1A2 gene and induction by 3-methylcholanthrene. A region of DNA that supports AH-receptor binding and promoter-specific induction |
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