Functional analyses of promoter elements responsible for the differential expression of the human metallothionein (MT)-IG and MT-IF genes
The sequences responsible for heavy metal-inducible expression are situated within the proximal 437 and 160 base pairs (bp) of MT-IF and MT-IG 5'-flanking sequence, respectively. Only 105 bp of proximal MT-IG 5'-flanking sequence containing a TATA box, two metal responsive elements (MREs),...
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| Veröffentlicht in: | The Journal of biological chemistry 1991-05, Vol.266 (15), p.9866-9875 |
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| description | The sequences responsible for heavy metal-inducible expression are situated within the proximal 437 and 160 base pairs (bp)
of MT-IF and MT-IG 5'-flanking sequence, respectively. Only 105 bp of proximal MT-IG 5'-flanking sequence containing a TATA
box, two metal responsive elements (MREs), and three GC motifs and 147 bp of proximal MT-IF 5'-flanking sequence containing
a TATCA box, four MREs, and two GC motifs were required for heavy metal-inducible expression. However, the proximal 111 bp
of MT-IF 5'-flanking sequences (a TATCA box, two MREs, and two GC motifs) was not responsive to heavy metals and competes
less efficiently than the 105-bp MT-IG fragment in a competition transfection analysis. The MT-IF promoter fragment containing
MREc and MREd is substantially stronger and a more efficient competitor than the MT-IG promoter fragment containing MREc and
MREd. Furthermore, the proximal 160 bp of MT-IG 5'-flanking sequence functions as a strong metal-inducible promoter but not
as a metal-inducible enhancer. Mobility shift analysis of MT-IF and MT-IG promoter subregions suggests a correlation between
protein binding to MRE sequences and MT gene expression. These data illustrate that the overall structural and functional
organization of the MT-IF and MT-IG promoters are very different and that the molecular mechanisms governing differential
expression levels of human MT genes are quite complex. |
| doi_str_mv | 10.1016/S0021-9258(18)92899-1 |
| format | Article |
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of MT-IF and MT-IG 5'-flanking sequence, respectively. Only 105 bp of proximal MT-IG 5'-flanking sequence containing a TATA
box, two metal responsive elements (MREs), and three GC motifs and 147 bp of proximal MT-IF 5'-flanking sequence containing
a TATCA box, four MREs, and two GC motifs were required for heavy metal-inducible expression. However, the proximal 111 bp
of MT-IF 5'-flanking sequences (a TATCA box, two MREs, and two GC motifs) was not responsive to heavy metals and competes
less efficiently than the 105-bp MT-IG fragment in a competition transfection analysis. The MT-IF promoter fragment containing
MREc and MREd is substantially stronger and a more efficient competitor than the MT-IG promoter fragment containing MREc and
MREd. Furthermore, the proximal 160 bp of MT-IG 5'-flanking sequence functions as a strong metal-inducible promoter but not
as a metal-inducible enhancer. Mobility shift analysis of MT-IF and MT-IG promoter subregions suggests a correlation between
protein binding to MRE sequences and MT gene expression. These data illustrate that the overall structural and functional
organization of the MT-IF and MT-IG promoters are very different and that the molecular mechanisms governing differential
expression levels of human MT genes are quite complex.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1016/S0021-9258(18)92899-1</identifier><identifier>PMID: 1903400</identifier><identifier>CODEN: JBCHA3</identifier><language>eng</language><publisher>Bethesda, MD: American Society for Biochemistry and Molecular Biology</publisher><subject>Base Sequence ; beta-Galactosidase - genetics ; Biological and medical sciences ; Chloramphenicol O-Acetyltransferase - genetics ; Chromosome Deletion ; DNA - genetics ; Enhancer Elements, Genetic ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation, Enzymologic ; genes ; Genes. Genome ; Humans ; Liver Neoplasms - enzymology ; Metallothionein - genetics ; metals ; Molecular and cellular biology ; Molecular genetics ; Molecular Sequence Data ; Plasmids ; Promoter Regions, Genetic ; promoters ; Transcription, Genetic ; Transfection ; Tumor Cells, Cultured</subject><ispartof>The Journal of biological chemistry, 1991-05, Vol.266 (15), p.9866-9875</ispartof><rights>1991 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-65eea6c2fc6202918e1d77a80b8c358f2a6efe8b9d1d42fef40037677c8c61ad3</citedby><cites>FETCH-LOGICAL-c440t-65eea6c2fc6202918e1d77a80b8c358f2a6efe8b9d1d42fef40037677c8c61ad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19737678$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1903400$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>FOSTER, R</creatorcontrib><creatorcontrib>GEDAMU, L</creatorcontrib><title>Functional analyses of promoter elements responsible for the differential expression of the human metallothionein (MT)-IG and MT-IF genes</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>The sequences responsible for heavy metal-inducible expression are situated within the proximal 437 and 160 base pairs (bp)
of MT-IF and MT-IG 5'-flanking sequence, respectively. Only 105 bp of proximal MT-IG 5'-flanking sequence containing a TATA
box, two metal responsive elements (MREs), and three GC motifs and 147 bp of proximal MT-IF 5'-flanking sequence containing
a TATCA box, four MREs, and two GC motifs were required for heavy metal-inducible expression. However, the proximal 111 bp
of MT-IF 5'-flanking sequences (a TATCA box, two MREs, and two GC motifs) was not responsive to heavy metals and competes
less efficiently than the 105-bp MT-IG fragment in a competition transfection analysis. The MT-IF promoter fragment containing
MREc and MREd is substantially stronger and a more efficient competitor than the MT-IG promoter fragment containing MREc and
MREd. Furthermore, the proximal 160 bp of MT-IG 5'-flanking sequence functions as a strong metal-inducible promoter but not
as a metal-inducible enhancer. Mobility shift analysis of MT-IF and MT-IG promoter subregions suggests a correlation between
protein binding to MRE sequences and MT gene expression. These data illustrate that the overall structural and functional
organization of the MT-IF and MT-IG promoters are very different and that the molecular mechanisms governing differential
expression levels of human MT genes are quite complex.</description><subject>Base Sequence</subject><subject>beta-Galactosidase - genetics</subject><subject>Biological and medical sciences</subject><subject>Chloramphenicol O-Acetyltransferase - genetics</subject><subject>Chromosome Deletion</subject><subject>DNA - genetics</subject><subject>Enhancer Elements, Genetic</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>genes</subject><subject>Genes. Genome</subject><subject>Humans</subject><subject>Liver Neoplasms - enzymology</subject><subject>Metallothionein - genetics</subject><subject>metals</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Molecular Sequence Data</subject><subject>Plasmids</subject><subject>Promoter Regions, Genetic</subject><subject>promoters</subject><subject>Transcription, Genetic</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkc1u1DAUhS0EKkPhESpZQqB2EbCdxLGXqGLKSK1YMEjsLMe5bowce7ATQR-Bt8bpjAAvrhfnO_cXoQtK3lFC-fsvhDBaSdaKSyquJBNSVvQJ2lAi6qpu6benaPMXeY5e5PydlNdIeobOqCR1Q8gG_d4uwcwuBu2xLuEhQ8bR4kOKU5whYfAwQZgzTpAPMWTXe8A2JjyPgAdnLaQiu2KHX4fC5JJrTbDK4zLpgCeYtfdxHosCLuDLu_1Vtbsp5QZ8t692W3wPAfJL9Mxqn-HV6T9HX7cf99efqtvPN7vrD7eVaRoyV7wF0NwwazgjTFIBdOg6LUgvTN0KyzQHC6KXAx0aZsGWMeuOd50RhlM91Ofo7TFvGfHHAnlWk8sGvNcB4pIVbWVLBGsL2B5Bk2LOCaw6JDfp9KAoUesJ1OMJ1LpfRYV6PIGixXdxKrD0Ewz_XMedF_3NSdfZaG-TDsbl_7Bu7VcU7vWRG939-NMlUL2LZoRJMc5Lm0oKzus_QVWcZQ</recordid><startdate>19910525</startdate><enddate>19910525</enddate><creator>FOSTER, R</creator><creator>GEDAMU, L</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>7T3</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>19910525</creationdate><title>Functional analyses of promoter elements responsible for the differential expression of the human metallothionein (MT)-IG and MT-IF genes</title><author>FOSTER, R ; GEDAMU, L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-65eea6c2fc6202918e1d77a80b8c358f2a6efe8b9d1d42fef40037677c8c61ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Base Sequence</topic><topic>beta-Galactosidase - genetics</topic><topic>Biological and medical sciences</topic><topic>Chloramphenicol O-Acetyltransferase - genetics</topic><topic>Chromosome Deletion</topic><topic>DNA - genetics</topic><topic>Enhancer Elements, Genetic</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>genes</topic><topic>Genes. Genome</topic><topic>Humans</topic><topic>Liver Neoplasms - enzymology</topic><topic>Metallothionein - genetics</topic><topic>metals</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Molecular Sequence Data</topic><topic>Plasmids</topic><topic>Promoter Regions, Genetic</topic><topic>promoters</topic><topic>Transcription, Genetic</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>FOSTER, R</creatorcontrib><creatorcontrib>GEDAMU, L</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>Human Genome Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>FOSTER, R</au><au>GEDAMU, L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional analyses of promoter elements responsible for the differential expression of the human metallothionein (MT)-IG and MT-IF genes</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1991-05-25</date><risdate>1991</risdate><volume>266</volume><issue>15</issue><spage>9866</spage><epage>9875</epage><pages>9866-9875</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><coden>JBCHA3</coden><abstract>The sequences responsible for heavy metal-inducible expression are situated within the proximal 437 and 160 base pairs (bp)
of MT-IF and MT-IG 5'-flanking sequence, respectively. Only 105 bp of proximal MT-IG 5'-flanking sequence containing a TATA
box, two metal responsive elements (MREs), and three GC motifs and 147 bp of proximal MT-IF 5'-flanking sequence containing
a TATCA box, four MREs, and two GC motifs were required for heavy metal-inducible expression. However, the proximal 111 bp
of MT-IF 5'-flanking sequences (a TATCA box, two MREs, and two GC motifs) was not responsive to heavy metals and competes
less efficiently than the 105-bp MT-IG fragment in a competition transfection analysis. The MT-IF promoter fragment containing
MREc and MREd is substantially stronger and a more efficient competitor than the MT-IG promoter fragment containing MREc and
MREd. Furthermore, the proximal 160 bp of MT-IG 5'-flanking sequence functions as a strong metal-inducible promoter but not
as a metal-inducible enhancer. Mobility shift analysis of MT-IF and MT-IG promoter subregions suggests a correlation between
protein binding to MRE sequences and MT gene expression. These data illustrate that the overall structural and functional
organization of the MT-IF and MT-IG promoters are very different and that the molecular mechanisms governing differential
expression levels of human MT genes are quite complex.</abstract><cop>Bethesda, MD</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>1903400</pmid><doi>10.1016/S0021-9258(18)92899-1</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Base Sequence beta-Galactosidase - genetics Biological and medical sciences Chloramphenicol O-Acetyltransferase - genetics Chromosome Deletion DNA - genetics Enhancer Elements, Genetic Fundamental and applied biological sciences. Psychology Gene Expression Regulation, Enzymologic genes Genes. Genome Humans Liver Neoplasms - enzymology Metallothionein - genetics metals Molecular and cellular biology Molecular genetics Molecular Sequence Data Plasmids Promoter Regions, Genetic promoters Transcription, Genetic Transfection Tumor Cells, Cultured |
| title | Functional analyses of promoter elements responsible for the differential expression of the human metallothionein (MT)-IG and MT-IF genes |
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