The Major G‑Quadruplex Formed in the Human BCL‑2 Proximal Promoter Adopts a Parallel Structure with a 13-nt Loop in K+ Solution
The human BCL-2 gene contains a 39-bp GC-rich region upstream of the P1 promoter that has been shown to be critically involved in the regulation of BCL-2 gene expression. Inhibition of BCL-2 expression can decrease cellular proliferation and enhance the efficacy of chemotherapy. Here we report the m...
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Veröffentlicht in: | Journal of the American Chemical Society 2014-02, Vol.136 (5), p.1750-1753 |
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description | The human BCL-2 gene contains a 39-bp GC-rich region upstream of the P1 promoter that has been shown to be critically involved in the regulation of BCL-2 gene expression. Inhibition of BCL-2 expression can decrease cellular proliferation and enhance the efficacy of chemotherapy. Here we report the major G-quadruplex formed in the Pu39 G-rich strand in this BCL-2 promoter region. The 1245G4 quadruplex adopts a parallel structure with one 13-nt and two 1-nt chain-reversal loops. The 1245G4 quadruplex involves four nonsuccessive G-runs, I, II, IV, V, unlike the previously reported bcl2 MidG4 quadruplex formed on the central four G-runs. The parallel 1245G4 quadruplex with the 13-nt loop, unexpectedly, appears to be more stable than the mixed parallel/antiparallel MidG4. Parallel-stranded structures with two 1-nt loops and one variable-length middle loop are found to be prevalent in the promoter G-quadruplexes; the variable middle loop is suggested to determine the specific overall structure and potential ligand recognition site. A limit of 7 nt in loop length is used in all quadruplex-predicting software. Thus, the formation and high stability of the 1245G4 quadruplex with a 13-nt loop is significant. The presence of two distinct interchangeable G-quadruplexes in the overlapping region of the BCL-2 promoter is intriguing, suggesting a novel mechanism for gene transcriptional regulation and ligand modulation. |
doi_str_mv | 10.1021/ja4118945 |
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Inhibition of BCL-2 expression can decrease cellular proliferation and enhance the efficacy of chemotherapy. Here we report the major G-quadruplex formed in the Pu39 G-rich strand in this BCL-2 promoter region. The 1245G4 quadruplex adopts a parallel structure with one 13-nt and two 1-nt chain-reversal loops. The 1245G4 quadruplex involves four nonsuccessive G-runs, I, II, IV, V, unlike the previously reported bcl2 MidG4 quadruplex formed on the central four G-runs. The parallel 1245G4 quadruplex with the 13-nt loop, unexpectedly, appears to be more stable than the mixed parallel/antiparallel MidG4. Parallel-stranded structures with two 1-nt loops and one variable-length middle loop are found to be prevalent in the promoter G-quadruplexes; the variable middle loop is suggested to determine the specific overall structure and potential ligand recognition site. A limit of 7 nt in loop length is used in all quadruplex-predicting software. Thus, the formation and high stability of the 1245G4 quadruplex with a 13-nt loop is significant. 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Am. Chem. Soc</addtitle><description>The human BCL-2 gene contains a 39-bp GC-rich region upstream of the P1 promoter that has been shown to be critically involved in the regulation of BCL-2 gene expression. Inhibition of BCL-2 expression can decrease cellular proliferation and enhance the efficacy of chemotherapy. Here we report the major G-quadruplex formed in the Pu39 G-rich strand in this BCL-2 promoter region. The 1245G4 quadruplex adopts a parallel structure with one 13-nt and two 1-nt chain-reversal loops. The 1245G4 quadruplex involves four nonsuccessive G-runs, I, II, IV, V, unlike the previously reported bcl2 MidG4 quadruplex formed on the central four G-runs. The parallel 1245G4 quadruplex with the 13-nt loop, unexpectedly, appears to be more stable than the mixed parallel/antiparallel MidG4. Parallel-stranded structures with two 1-nt loops and one variable-length middle loop are found to be prevalent in the promoter G-quadruplexes; the variable middle loop is suggested to determine the specific overall structure and potential ligand recognition site. A limit of 7 nt in loop length is used in all quadruplex-predicting software. Thus, the formation and high stability of the 1245G4 quadruplex with a 13-nt loop is significant. The presence of two distinct interchangeable G-quadruplexes in the overlapping region of the BCL-2 promoter is intriguing, suggesting a novel mechanism for gene transcriptional regulation and ligand modulation.</description><subject>Base Sequence</subject><subject>Communication</subject><subject>G-Quadruplexes</subject><subject>Genes, bcl-2</subject><subject>Guanine - chemistry</subject><subject>Humans</subject><subject>Molecular Sequence Data</subject><subject>Nuclear Magnetic Resonance, Biomolecular</subject><subject>Nucleic Acid Conformation</subject><subject>Potassium - chemistry</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Folding</subject><subject>Proto-Oncogene Proteins c-bcl-2 - chemistry</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Solutions</subject><issn>0002-7863</issn><issn>1520-5126</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>N~.</sourceid><sourceid>EIF</sourceid><recordid>eNptkcFOwyAYgInR6JwefAHDxYMxVaDQdheTubjNWOPM5pnQlro2XWko6LyZ-AS-ok8iy3TRRC7A_3988PMDcITROUYEX5SCYhz1KNsCHcwI8hgmwTboIISIF0aBvwf227Z0W0oivAv2CKUMRRHqgPfZXMI7USoNR59vHw9WZNo2lVzCodILmcGihsYhY7sQNbwaxA4icKLVsliIarVYKCM17GeqMS0UcCK0qCpZwanRNjVWS_hSmLnLYN-rDYyValbS2zM4VZU1haoPwE4uqlYefs9d8Di8ng3GXnw_uhn0Y09QxIxHKclZIntJ6gahhDKaiECEuCd9EQU5DrIwoUnq5z7xkQuRIBKY4DDHKMxcvAsu197GJq60VNbGvZU32pWiX7kSBf-bqYs5f1LPnIbOyKgTnK4FqVZtq2W-OYsRX3WCbzrh2OPfl23In693wMkaEGnLS2V17Wr_R_QF3oWRsg</recordid><startdate>20140205</startdate><enddate>20140205</enddate><creator>Agrawal, Prashansa</creator><creator>Lin, Clement</creator><creator>Mathad, Raveendra I</creator><creator>Carver, Megan</creator><creator>Yang, Danzhou</creator><general>American Chemical Society</general><scope>N~.</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>5PM</scope></search><sort><creationdate>20140205</creationdate><title>The Major G‑Quadruplex Formed in the Human BCL‑2 Proximal Promoter Adopts a Parallel Structure with a 13-nt Loop in K+ Solution</title><author>Agrawal, Prashansa ; Lin, Clement ; Mathad, Raveendra I ; Carver, Megan ; Yang, Danzhou</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a405t-442f5be9bcccc242454ba6a719e3a86f16d7b4bc3f32303a8268a1217f107dbc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Base Sequence</topic><topic>Communication</topic><topic>G-Quadruplexes</topic><topic>Genes, bcl-2</topic><topic>Guanine - chemistry</topic><topic>Humans</topic><topic>Molecular Sequence Data</topic><topic>Nuclear Magnetic Resonance, Biomolecular</topic><topic>Nucleic Acid Conformation</topic><topic>Potassium - chemistry</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Folding</topic><topic>Proto-Oncogene Proteins c-bcl-2 - chemistry</topic><topic>Proto-Oncogene Proteins c-bcl-2 - genetics</topic><topic>Solutions</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Agrawal, Prashansa</creatorcontrib><creatorcontrib>Lin, Clement</creatorcontrib><creatorcontrib>Mathad, Raveendra I</creatorcontrib><creatorcontrib>Carver, Megan</creatorcontrib><creatorcontrib>Yang, Danzhou</creatorcontrib><collection>American Chemical Society (ACS) Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of the American Chemical Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Agrawal, Prashansa</au><au>Lin, Clement</au><au>Mathad, Raveendra I</au><au>Carver, Megan</au><au>Yang, Danzhou</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Major G‑Quadruplex Formed in the Human BCL‑2 Proximal Promoter Adopts a Parallel Structure with a 13-nt Loop in K+ Solution</atitle><jtitle>Journal of the American Chemical Society</jtitle><addtitle>J. Am. Chem. Soc</addtitle><date>2014-02-05</date><risdate>2014</risdate><volume>136</volume><issue>5</issue><spage>1750</spage><epage>1753</epage><pages>1750-1753</pages><issn>0002-7863</issn><eissn>1520-5126</eissn><abstract>The human BCL-2 gene contains a 39-bp GC-rich region upstream of the P1 promoter that has been shown to be critically involved in the regulation of BCL-2 gene expression. Inhibition of BCL-2 expression can decrease cellular proliferation and enhance the efficacy of chemotherapy. Here we report the major G-quadruplex formed in the Pu39 G-rich strand in this BCL-2 promoter region. The 1245G4 quadruplex adopts a parallel structure with one 13-nt and two 1-nt chain-reversal loops. The 1245G4 quadruplex involves four nonsuccessive G-runs, I, II, IV, V, unlike the previously reported bcl2 MidG4 quadruplex formed on the central four G-runs. The parallel 1245G4 quadruplex with the 13-nt loop, unexpectedly, appears to be more stable than the mixed parallel/antiparallel MidG4. Parallel-stranded structures with two 1-nt loops and one variable-length middle loop are found to be prevalent in the promoter G-quadruplexes; the variable middle loop is suggested to determine the specific overall structure and potential ligand recognition site. A limit of 7 nt in loop length is used in all quadruplex-predicting software. Thus, the formation and high stability of the 1245G4 quadruplex with a 13-nt loop is significant. The presence of two distinct interchangeable G-quadruplexes in the overlapping region of the BCL-2 promoter is intriguing, suggesting a novel mechanism for gene transcriptional regulation and ligand modulation.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>24450880</pmid><doi>10.1021/ja4118945</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Base Sequence Communication G-Quadruplexes Genes, bcl-2 Guanine - chemistry Humans Molecular Sequence Data Nuclear Magnetic Resonance, Biomolecular Nucleic Acid Conformation Potassium - chemistry Promoter Regions, Genetic Protein Folding Proto-Oncogene Proteins c-bcl-2 - chemistry Proto-Oncogene Proteins c-bcl-2 - genetics Solutions |
title | The Major G‑Quadruplex Formed in the Human BCL‑2 Proximal Promoter Adopts a Parallel Structure with a 13-nt Loop in K+ Solution |
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