A major positive regulatory region located far upstream of the human α-globin gene locus
We have identified a remote, tissue-specific, positive regulatory element that is of major importance in determining the level of human alpha-globin gene expression. Stable transformants containing this DNA segment linked to the alpha gene in mouse erythroleukemia cells expressed human alpha mRNA at...
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| Veröffentlicht in: | Genes & development 1990-09, Vol.4 (9), p.1588-1601 |
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| container_title | Genes & development |
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| creator | HIGGS, D. R WOOD, W. G JARMAN, A. P SHARPE, J LIDA, J PRETORIUS, I.-M AYYUB, H |
| description | We have identified a remote, tissue-specific, positive regulatory element that is of major importance in determining the level of human alpha-globin gene expression. Stable transformants containing this DNA segment linked to the alpha gene in mouse erythroleukemia cells expressed human alpha mRNA at levels that are indistinguishable from those seen in interspecific hybrids containing the human alpha genes in their normal context on chromosome 16. Furthermore, all transgenic mice containing the alpha genes linked to this region expressed alpha-globin mRNA at high levels in erythroid tissues; and in one such mouse, readily detectable levels of human alpha-globin chains could be demonstrated in the peripheral blood. There is considerable similarity in the position, structure, and function of this region upstream of the alpha-globin complex with previously described elements within the beta-globin dominant control region (DCR). This is m marked contrast to other structural and functional differences between the two gene clusters. It seems likely that these critical, positive regulatory regions might provide target sequences through which coordinate regulation of the alpha- and beta-like globin genes is achieved. |
| doi_str_mv | 10.1101/gad.4.9.1588 |
| format | Article |
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R ; WOOD, W. G ; JARMAN, A. P ; SHARPE, J ; LIDA, J ; PRETORIUS, I.-M ; AYYUB, H</creator><creatorcontrib>HIGGS, D. R ; WOOD, W. G ; JARMAN, A. P ; SHARPE, J ; LIDA, J ; PRETORIUS, I.-M ; AYYUB, H</creatorcontrib><description>We have identified a remote, tissue-specific, positive regulatory element that is of major importance in determining the level of human alpha-globin gene expression. Stable transformants containing this DNA segment linked to the alpha gene in mouse erythroleukemia cells expressed human alpha mRNA at levels that are indistinguishable from those seen in interspecific hybrids containing the human alpha genes in their normal context on chromosome 16. Furthermore, all transgenic mice containing the alpha genes linked to this region expressed alpha-globin mRNA at high levels in erythroid tissues; and in one such mouse, readily detectable levels of human alpha-globin chains could be demonstrated in the peripheral blood. There is considerable similarity in the position, structure, and function of this region upstream of the alpha-globin complex with previously described elements within the beta-globin dominant control region (DCR). This is m marked contrast to other structural and functional differences between the two gene clusters. It seems likely that these critical, positive regulatory regions might provide target sequences through which coordinate regulation of the alpha- and beta-like globin genes is achieved.</description><identifier>ISSN: 0890-9369</identifier><identifier>EISSN: 1549-5477</identifier><identifier>DOI: 10.1101/gad.4.9.1588</identifier><identifier>PMID: 2253879</identifier><identifier>CODEN: GEDEEP</identifier><language>eng</language><publisher>Cold Spring Harbor, NY: Cold Spring Harbor Laboratory</publisher><subject>Animals ; Biological and medical sciences ; Deoxyribonuclease I ; Erythrocytes - metabolism ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation - genetics ; genes ; Globins - genetics ; Humans ; Leukemia, Erythroblastic, Acute ; loci ; Mice ; Mice, Transgenic ; Molecular and cellular biology ; Molecular genetics ; Multigene Family ; Organ Specificity ; Regulatory Sequences, Nucleic Acid ; Transcription. Transcription factor. Splicing. Rna processing ; Transfection ; Tumor Cells, Cultured</subject><ispartof>Genes & development, 1990-09, Vol.4 (9), p.1588-1601</ispartof><rights>1991 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-44261a6905e14245a998c68e4d67de70f031edbf2254a276fd1a29aa68c5faa53</citedby><cites>FETCH-LOGICAL-c451t-44261a6905e14245a998c68e4d67de70f031edbf2254a276fd1a29aa68c5faa53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19278271$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2253879$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HIGGS, D. R</creatorcontrib><creatorcontrib>WOOD, W. G</creatorcontrib><creatorcontrib>JARMAN, A. P</creatorcontrib><creatorcontrib>SHARPE, J</creatorcontrib><creatorcontrib>LIDA, J</creatorcontrib><creatorcontrib>PRETORIUS, I.-M</creatorcontrib><creatorcontrib>AYYUB, H</creatorcontrib><title>A major positive regulatory region located far upstream of the human α-globin gene locus</title><title>Genes & development</title><addtitle>Genes Dev</addtitle><description>We have identified a remote, tissue-specific, positive regulatory element that is of major importance in determining the level of human alpha-globin gene expression. Stable transformants containing this DNA segment linked to the alpha gene in mouse erythroleukemia cells expressed human alpha mRNA at levels that are indistinguishable from those seen in interspecific hybrids containing the human alpha genes in their normal context on chromosome 16. Furthermore, all transgenic mice containing the alpha genes linked to this region expressed alpha-globin mRNA at high levels in erythroid tissues; and in one such mouse, readily detectable levels of human alpha-globin chains could be demonstrated in the peripheral blood. There is considerable similarity in the position, structure, and function of this region upstream of the alpha-globin complex with previously described elements within the beta-globin dominant control region (DCR). This is m marked contrast to other structural and functional differences between the two gene clusters. It seems likely that these critical, positive regulatory regions might provide target sequences through which coordinate regulation of the alpha- and beta-like globin genes is achieved.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Deoxyribonuclease I</subject><subject>Erythrocytes - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation - genetics</subject><subject>genes</subject><subject>Globins - genetics</subject><subject>Humans</subject><subject>Leukemia, Erythroblastic, Acute</subject><subject>loci</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Multigene Family</subject><subject>Organ Specificity</subject><subject>Regulatory Sequences, Nucleic Acid</subject><subject>Transcription. Transcription factor. Splicing. Rna processing</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><issn>0890-9369</issn><issn>1549-5477</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1990</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1LxDAQhoMouq7evAq56MmuSZvPo4hfIHjRg6cw207WStusSSvsz_KP-JvssosePc3A-8zL8BBywtmMc8YvF1DNxMzOuDRmh0y4FDaTQutdMmHGsswWyh6Qw5TeGWOKKbVP9vNcFkbbCXm9oi28h0iXIdV9_Yk04mJooA9xtV7r0NEmlNBjRT1EOixTHxFaGjzt35C-DS109PsrWzRhXnd0gR2uD4Z0RPY8NAmPt3NKXm5vnq_vs8enu4frq8esFJL3mRC54qAsk8hFLiRYa0plUFRKV6iZZwXHau7HjwXkWvmKQ24BlCmlB5DFlJxvepcxfAyYetfWqcSmgQ7DkJxhXDFr_we51OMvmo3gxQYsY0gponfLWLcQV44zt1buRuVOOOvWykf8dNs7zFusfuGt4zE_2-aQSmh8hK6s01-nzbXJNS9-AIHNifs</recordid><startdate>19900901</startdate><enddate>19900901</enddate><creator>HIGGS, D. R</creator><creator>WOOD, W. G</creator><creator>JARMAN, A. P</creator><creator>SHARPE, J</creator><creator>LIDA, J</creator><creator>PRETORIUS, I.-M</creator><creator>AYYUB, H</creator><general>Cold Spring Harbor Laboratory</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><scope>7X8</scope></search><sort><creationdate>19900901</creationdate><title>A major positive regulatory region located far upstream of the human α-globin gene locus</title><author>HIGGS, D. R ; WOOD, W. G ; JARMAN, A. P ; SHARPE, J ; LIDA, J ; PRETORIUS, I.-M ; AYYUB, H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-44261a6905e14245a998c68e4d67de70f031edbf2254a276fd1a29aa68c5faa53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1990</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Deoxyribonuclease I</topic><topic>Erythrocytes - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation - genetics</topic><topic>genes</topic><topic>Globins - genetics</topic><topic>Humans</topic><topic>Leukemia, Erythroblastic, Acute</topic><topic>loci</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Multigene Family</topic><topic>Organ Specificity</topic><topic>Regulatory Sequences, 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>HIGGS, D. R</creatorcontrib><creatorcontrib>WOOD, W. G</creatorcontrib><creatorcontrib>JARMAN, A. P</creatorcontrib><creatorcontrib>SHARPE, J</creatorcontrib><creatorcontrib>LIDA, J</creatorcontrib><creatorcontrib>PRETORIUS, I.-M</creatorcontrib><creatorcontrib>AYYUB, 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>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><collection>MEDLINE - Academic</collection><jtitle>Genes & development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HIGGS, D. R</au><au>WOOD, W. G</au><au>JARMAN, A. P</au><au>SHARPE, J</au><au>LIDA, J</au><au>PRETORIUS, I.-M</au><au>AYYUB, H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A major positive regulatory region located far upstream of the human α-globin gene locus</atitle><jtitle>Genes & development</jtitle><addtitle>Genes Dev</addtitle><date>1990-09-01</date><risdate>1990</risdate><volume>4</volume><issue>9</issue><spage>1588</spage><epage>1601</epage><pages>1588-1601</pages><issn>0890-9369</issn><eissn>1549-5477</eissn><coden>GEDEEP</coden><abstract>We have identified a remote, tissue-specific, positive regulatory element that is of major importance in determining the level of human alpha-globin gene expression. Stable transformants containing this DNA segment linked to the alpha gene in mouse erythroleukemia cells expressed human alpha mRNA at levels that are indistinguishable from those seen in interspecific hybrids containing the human alpha genes in their normal context on chromosome 16. Furthermore, all transgenic mice containing the alpha genes linked to this region expressed alpha-globin mRNA at high levels in erythroid tissues; and in one such mouse, readily detectable levels of human alpha-globin chains could be demonstrated in the peripheral blood. There is considerable similarity in the position, structure, and function of this region upstream of the alpha-globin complex with previously described elements within the beta-globin dominant control region (DCR). This is m marked contrast to other structural and functional differences between the two gene clusters. It seems likely that these critical, positive regulatory regions might provide target sequences through which coordinate regulation of the alpha- and beta-like globin genes is achieved.</abstract><cop>Cold Spring Harbor, NY</cop><pub>Cold Spring Harbor Laboratory</pub><pmid>2253879</pmid><doi>10.1101/gad.4.9.1588</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Biological and medical sciences Deoxyribonuclease I Erythrocytes - metabolism Fundamental and applied biological sciences. Psychology Gene Expression Regulation - genetics genes Globins - genetics Humans Leukemia, Erythroblastic, Acute loci Mice Mice, Transgenic Molecular and cellular biology Molecular genetics Multigene Family Organ Specificity Regulatory Sequences, Nucleic Acid Transcription. Transcription factor. Splicing. Rna processing Transfection Tumor Cells, Cultured |
| title | A major positive regulatory region located far upstream of the human α-globin gene locus |
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