Transcriptional regulation of the murine erythroid-specific 5-aminolevulinate synthase gene
5-Aminolevulinate synthase (ALAS) catalyzes the first step of the heme biosynthetic pathway in mammalian cells. Separate genes encode the two isoforms: ubiquitously expressed ALAS (ALAS1) and erythroid-specific ALAS (ALAS2). Transcription of the ALAS2 gene is only activated during erythroid cell dif...
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| Veröffentlicht in: | Gene 2000-04, Vol.247 (1), p.153-166 |
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| creator | Kramer, Marianne F Gunaratne, Prabha Ferreira, Gloria C |
| description | 5-Aminolevulinate synthase (ALAS) catalyzes the first step of the heme biosynthetic pathway in mammalian cells. Separate genes encode the two isoforms: ubiquitously expressed ALAS (ALAS1) and erythroid-specific ALAS (ALAS2). Transcription of the
ALAS2 gene is only activated during erythroid cell differentiation. This stimulation allows for the formation of hemoglobin-specific heme. The 5′-flanking region of the mouse
ALAS2 gene was studied in order to define its erythroid-specific function in transcriptional activation. Putative binding sites for the erythroid-specific nuclear factors GATA-1, NF-E2, and EKLF were identified within the first 300
bp region of the mouse
ALAS2 5′-flanking region. However, this 300
bp region alone did not efficiently activate transient expression in erythroid MEL and K562 cell lines. Additional DNA regulatory sequences found within 300–718
bp upstream of the transcription start site were required for maximal transcriptional activation, even though these regions stimulated similar expression in the non-erythroid HeLa and NIH/3T3 cells. This suggests that
cis-acting elements present in the 5′-flanking region are not responsible for maintenance of transcriptional silencing in non-erythroid cell lines and that tissue-specific regulation of
ALAS2 depends on other regions of the gene or on chromatin remodeling. A putative hypoxia inducible factor 1 (HIF-1) response element was identified within the 300–718
bp upstream region. Significantly, two proximal GATA-1-binding sites (−118/−113 and −98/−93) and a region located within −518 to −315
bp of the mouse
ALAS2 promoter were essential for transcriptional activation during chemically induced differentiation of MEL cells, implying their importance in conferring erythroid specificity to the
ALAS2 transcriptional activation. This is the first study to delimit the
cis-acting region responsible for activation of the ALAS2 promoter upon dimethyl-sulfoxide induction in MEL cells. |
| doi_str_mv | 10.1016/S0378-1119(00)00103-7 |
| format | Article |
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ALAS2 gene is only activated during erythroid cell differentiation. This stimulation allows for the formation of hemoglobin-specific heme. The 5′-flanking region of the mouse
ALAS2 gene was studied in order to define its erythroid-specific function in transcriptional activation. Putative binding sites for the erythroid-specific nuclear factors GATA-1, NF-E2, and EKLF were identified within the first 300
bp region of the mouse
ALAS2 5′-flanking region. However, this 300
bp region alone did not efficiently activate transient expression in erythroid MEL and K562 cell lines. Additional DNA regulatory sequences found within 300–718
bp upstream of the transcription start site were required for maximal transcriptional activation, even though these regions stimulated similar expression in the non-erythroid HeLa and NIH/3T3 cells. This suggests that
cis-acting elements present in the 5′-flanking region are not responsible for maintenance of transcriptional silencing in non-erythroid cell lines and that tissue-specific regulation of
ALAS2 depends on other regions of the gene or on chromatin remodeling. A putative hypoxia inducible factor 1 (HIF-1) response element was identified within the 300–718
bp upstream region. Significantly, two proximal GATA-1-binding sites (−118/−113 and −98/−93) and a region located within −518 to −315
bp of the mouse
ALAS2 promoter were essential for transcriptional activation during chemically induced differentiation of MEL cells, implying their importance in conferring erythroid specificity to the
ALAS2 transcriptional activation. This is the first study to delimit the
cis-acting region responsible for activation of the ALAS2 promoter upon dimethyl-sulfoxide induction in MEL cells.</description><identifier>ISSN: 0378-1119</identifier><identifier>EISSN: 1879-0038</identifier><identifier>DOI: 10.1016/S0378-1119(00)00103-7</identifier><identifier>PMID: 10773455</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>3T3 Cells ; 5-Aminolevulinate Synthetase - genetics ; ALAS2 gene ; Animals ; Base Sequence ; Binding Sites - genetics ; Conserved Sequence ; dimethylsulfoxide ; DNA - chemistry ; DNA - genetics ; DNA - metabolism ; Erythrocytes - enzymology ; Gene Expression Regulation, Enzymologic ; HeLa Cells ; Heme biosynthesis ; Humans ; K562 Cells ; Luciferases - genetics ; Luciferases - metabolism ; Mice ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutation ; Promoter ; Promoter Regions, Genetic - genetics ; Recombinant Fusion Proteins - genetics ; Recombinant Fusion Proteins - metabolism ; Regulatory sequences ; Regulatory Sequences, Nucleic Acid ; Sequence Analysis, DNA ; Trans-Activators - metabolism ; Transcription, Genetic ; Transcriptional factors ; Tumor Cells, Cultured</subject><ispartof>Gene, 2000-04, Vol.247 (1), p.153-166</ispartof><rights>2000 Elsevier Science B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c510t-46c04b24a12e84c2f9dd31e9fa3d66ebe678db03e4e7d5230aea61dcc39575e83</citedby><cites>FETCH-LOGICAL-c510t-46c04b24a12e84c2f9dd31e9fa3d66ebe678db03e4e7d5230aea61dcc39575e83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0378-1119(00)00103-7$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10773455$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kramer, Marianne F</creatorcontrib><creatorcontrib>Gunaratne, Prabha</creatorcontrib><creatorcontrib>Ferreira, Gloria C</creatorcontrib><title>Transcriptional regulation of the murine erythroid-specific 5-aminolevulinate synthase gene</title><title>Gene</title><addtitle>Gene</addtitle><description>5-Aminolevulinate synthase (ALAS) catalyzes the first step of the heme biosynthetic pathway in mammalian cells. Separate genes encode the two isoforms: ubiquitously expressed ALAS (ALAS1) and erythroid-specific ALAS (ALAS2). Transcription of the
ALAS2 gene is only activated during erythroid cell differentiation. This stimulation allows for the formation of hemoglobin-specific heme. The 5′-flanking region of the mouse
ALAS2 gene was studied in order to define its erythroid-specific function in transcriptional activation. Putative binding sites for the erythroid-specific nuclear factors GATA-1, NF-E2, and EKLF were identified within the first 300
bp region of the mouse
ALAS2 5′-flanking region. However, this 300
bp region alone did not efficiently activate transient expression in erythroid MEL and K562 cell lines. Additional DNA regulatory sequences found within 300–718
bp upstream of the transcription start site were required for maximal transcriptional activation, even though these regions stimulated similar expression in the non-erythroid HeLa and NIH/3T3 cells. This suggests that
cis-acting elements present in the 5′-flanking region are not responsible for maintenance of transcriptional silencing in non-erythroid cell lines and that tissue-specific regulation of
ALAS2 depends on other regions of the gene or on chromatin remodeling. A putative hypoxia inducible factor 1 (HIF-1) response element was identified within the 300–718
bp upstream region. Significantly, two proximal GATA-1-binding sites (−118/−113 and −98/−93) and a region located within −518 to −315
bp of the mouse
ALAS2 promoter were essential for transcriptional activation during chemically induced differentiation of MEL cells, implying their importance in conferring erythroid specificity to the
ALAS2 transcriptional activation. This is the first study to delimit the
cis-acting region responsible for activation of the ALAS2 promoter upon dimethyl-sulfoxide induction in MEL cells.</description><subject>3T3 Cells</subject><subject>5-Aminolevulinate Synthetase - genetics</subject><subject>ALAS2 gene</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Binding Sites - genetics</subject><subject>Conserved Sequence</subject><subject>dimethylsulfoxide</subject><subject>DNA - chemistry</subject><subject>DNA - genetics</subject><subject>DNA - metabolism</subject><subject>Erythrocytes - enzymology</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>HeLa Cells</subject><subject>Heme biosynthesis</subject><subject>Humans</subject><subject>K562 Cells</subject><subject>Luciferases - genetics</subject><subject>Luciferases - metabolism</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis, Site-Directed</subject><subject>Mutation</subject><subject>Promoter</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Regulatory sequences</subject><subject>Regulatory Sequences, Nucleic Acid</subject><subject>Sequence Analysis, DNA</subject><subject>Trans-Activators - metabolism</subject><subject>Transcription, Genetic</subject><subject>Transcriptional factors</subject><subject>Tumor Cells, Cultured</subject><issn>0378-1119</issn><issn>1879-0038</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1Lw0AQhhdRbK3-BCUn0UN0NpvNJieR4hcUPFhPHpbt7qRdSTZ1Nyn035s2It6cyzDwvDPMQ8g5hRsKNLt9AybymFJaXAFcA1BgsTggY5qLIgZg-SEZ_yIjchLCJ_TFeXJMRhSEYCnnY_Ix98oF7e26tY1TVeRx2VVqN0RNGbUrjOrOW4cR-m278o01cVijtqXVEY9VbV1T4aarrFMtRmHr2pUKGC3R4Sk5KlUV8OynT8j748N8-hzPXp9epvezWHMKbZxmGtJFkiqaYJ7qpCyMYRSLUjGTZbjATORmAQxTFIYnDBSqjBqtWcEFx5xNyOWwd-2brw5DK2sbNFaVcth0QVLBaZHnrAf5AGrfhOCxlGtva-W3koLcWZV7q3KnTALIvVUp-tzFz4FuUaP5kxo09sDdAGD_5sail0FbdBqN9ahbaRr7z4lvPN6I7w</recordid><startdate>20000418</startdate><enddate>20000418</enddate><creator>Kramer, Marianne F</creator><creator>Gunaratne, Prabha</creator><creator>Ferreira, Gloria C</creator><general>Elsevier B.V</general><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>20000418</creationdate><title>Transcriptional regulation of the murine erythroid-specific 5-aminolevulinate synthase gene</title><author>Kramer, Marianne F ; Gunaratne, Prabha ; Ferreira, Gloria C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c510t-46c04b24a12e84c2f9dd31e9fa3d66ebe678db03e4e7d5230aea61dcc39575e83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>3T3 Cells</topic><topic>5-Aminolevulinate Synthetase - genetics</topic><topic>ALAS2 gene</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Binding Sites - genetics</topic><topic>Conserved Sequence</topic><topic>dimethylsulfoxide</topic><topic>DNA - chemistry</topic><topic>DNA - genetics</topic><topic>DNA - metabolism</topic><topic>Erythrocytes - enzymology</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>HeLa Cells</topic><topic>Heme biosynthesis</topic><topic>Humans</topic><topic>K562 Cells</topic><topic>Luciferases - genetics</topic><topic>Luciferases - metabolism</topic><topic>Mice</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis, Site-Directed</topic><topic>Mutation</topic><topic>Promoter</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Regulatory sequences</topic><topic>Regulatory Sequences, Nucleic Acid</topic><topic>Sequence Analysis, DNA</topic><topic>Trans-Activators - metabolism</topic><topic>Transcription, Genetic</topic><topic>Transcriptional factors</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kramer, Marianne F</creatorcontrib><creatorcontrib>Gunaratne, Prabha</creatorcontrib><creatorcontrib>Ferreira, Gloria C</creatorcontrib><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>Gene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kramer, Marianne F</au><au>Gunaratne, Prabha</au><au>Ferreira, Gloria C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptional regulation of the murine erythroid-specific 5-aminolevulinate synthase gene</atitle><jtitle>Gene</jtitle><addtitle>Gene</addtitle><date>2000-04-18</date><risdate>2000</risdate><volume>247</volume><issue>1</issue><spage>153</spage><epage>166</epage><pages>153-166</pages><issn>0378-1119</issn><eissn>1879-0038</eissn><abstract>5-Aminolevulinate synthase (ALAS) catalyzes the first step of the heme biosynthetic pathway in mammalian cells. Separate genes encode the two isoforms: ubiquitously expressed ALAS (ALAS1) and erythroid-specific ALAS (ALAS2). Transcription of the
ALAS2 gene is only activated during erythroid cell differentiation. This stimulation allows for the formation of hemoglobin-specific heme. The 5′-flanking region of the mouse
ALAS2 gene was studied in order to define its erythroid-specific function in transcriptional activation. Putative binding sites for the erythroid-specific nuclear factors GATA-1, NF-E2, and EKLF were identified within the first 300
bp region of the mouse
ALAS2 5′-flanking region. However, this 300
bp region alone did not efficiently activate transient expression in erythroid MEL and K562 cell lines. Additional DNA regulatory sequences found within 300–718
bp upstream of the transcription start site were required for maximal transcriptional activation, even though these regions stimulated similar expression in the non-erythroid HeLa and NIH/3T3 cells. This suggests that
cis-acting elements present in the 5′-flanking region are not responsible for maintenance of transcriptional silencing in non-erythroid cell lines and that tissue-specific regulation of
ALAS2 depends on other regions of the gene or on chromatin remodeling. A putative hypoxia inducible factor 1 (HIF-1) response element was identified within the 300–718
bp upstream region. Significantly, two proximal GATA-1-binding sites (−118/−113 and −98/−93) and a region located within −518 to −315
bp of the mouse
ALAS2 promoter were essential for transcriptional activation during chemically induced differentiation of MEL cells, implying their importance in conferring erythroid specificity to the
ALAS2 transcriptional activation. This is the first study to delimit the
cis-acting region responsible for activation of the ALAS2 promoter upon dimethyl-sulfoxide induction in MEL cells.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>10773455</pmid><doi>10.1016/S0378-1119(00)00103-7</doi><tpages>14</tpages></addata></record> |
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| ispartof | Gene, 2000-04, Vol.247 (1), p.153-166 |
| issn | 0378-1119 1879-0038 |
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| recordid | cdi_proquest_miscellaneous_17519883 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | 3T3 Cells 5-Aminolevulinate Synthetase - genetics ALAS2 gene Animals Base Sequence Binding Sites - genetics Conserved Sequence dimethylsulfoxide DNA - chemistry DNA - genetics DNA - metabolism Erythrocytes - enzymology Gene Expression Regulation, Enzymologic HeLa Cells Heme biosynthesis Humans K562 Cells Luciferases - genetics Luciferases - metabolism Mice Molecular Sequence Data Mutagenesis, Site-Directed Mutation Promoter Promoter Regions, Genetic - genetics Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism Regulatory sequences Regulatory Sequences, Nucleic Acid Sequence Analysis, DNA Trans-Activators - metabolism Transcription, Genetic Transcriptional factors Tumor Cells, Cultured |
| title | Transcriptional regulation of the murine erythroid-specific 5-aminolevulinate synthase gene |
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