Expression analysis using DNA microarrays demonstrates that E2F-1 up-regulates expression of DNA replication genes including replication protein A2
The transcription factor E2F-1 plays a pivotal role in the regulation of G1/S transition in higher eukaryotes cell cycle. We used a cell line containing an inducible E2F-1 and oligonucleotide microarray analysis to identify novel E2F target genes. We show that E2F-1 up-regulates the expression of a...
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description | The transcription factor E2F-1 plays a pivotal role in the regulation of G1/S transition in higher eukaryotes cell cycle. We used a cell line containing an inducible E2F-1 and oligonucleotide microarray analysis to identify novel E2F target genes. We show that E2F-1 up-regulates the expression of a number of genes coding for components of the DNA replication machinery. Among them is the gene coding for the 32 Kd subunit of replication protein A (RPA2). Replication protein A is the most abundant single strand DNA binding complex and it is essential for DNA replication. We demonstrate that RPA2 is a novel E2F target gene whose expression can be directly regulated by E2F-1 via E2F binding sites in its promoter. In addition, expression of Topoisomerase IIalpha and subunit IV of DNA polymerase alpha is also up-regulated upon E2F-1 induction. Taken together, these results provide novel links between components of the DNA replication machinery and the cell growth regulatory pathway involving the Rb tumor suppressor and E2F. |
doi_str_mv | 10.1038/sj.onc.1204230 |
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We used a cell line containing an inducible E2F-1 and oligonucleotide microarray analysis to identify novel E2F target genes. We show that E2F-1 up-regulates the expression of a number of genes coding for components of the DNA replication machinery. Among them is the gene coding for the 32 Kd subunit of replication protein A (RPA2). Replication protein A is the most abundant single strand DNA binding complex and it is essential for DNA replication. We demonstrate that RPA2 is a novel E2F target gene whose expression can be directly regulated by E2F-1 via E2F binding sites in its promoter. In addition, expression of Topoisomerase IIalpha and subunit IV of DNA polymerase alpha is also up-regulated upon E2F-1 induction. Taken together, these results provide novel links between components of the DNA replication machinery and the cell growth regulatory pathway involving the Rb tumor suppressor and E2F.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1204230</identifier><identifier>PMID: 11313881</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing</publisher><subject>Antigens, Neoplasm ; Base Sequence ; Binding sites ; Biological and medical sciences ; Carrier Proteins ; Cell cycle ; Cell Cycle Proteins ; Cell cycle, cell proliferation ; Cell growth ; Cell physiology ; Deoxyribonucleic acid ; DNA ; DNA biosynthesis ; DNA microarrays ; DNA polymerase ; DNA Polymerase I - biosynthesis ; DNA Replication - genetics ; DNA Topoisomerases, Type II - biosynthesis ; DNA-Binding Proteins - biosynthesis ; DNA-Binding Proteins - genetics ; DNA-directed DNA polymerase ; E2F protein ; E2F Transcription Factors ; E2F-1 protein ; E2F1 protein ; E2F1 Transcription Factor ; Fundamental and applied biological sciences. Psychology ; Gene Expression Profiling ; Genes ; Humans ; Isoenzymes - biosynthesis ; Kinases ; Molecular and cellular biology ; Molecular Sequence Data ; Oligonucleotide Array Sequence Analysis ; Oligonucleotides ; Promoter Regions, Genetic ; Protein Subunits ; Proteins ; RB protein ; Replication Protein A ; Retinoblastoma-Binding Protein 1 ; Transcription Factor DP1 ; Transcription Factors - metabolism ; Tumor suppressor genes ; Tumors ; Up-Regulation</subject><ispartof>Oncogene, 2001-03, Vol.20 (11), p.1379-1387</ispartof><rights>2001 INIST-CNRS</rights><rights>COPYRIGHT 2001 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Mar 15, 2001</rights><rights>Macmillan Publishers Limited 2001.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c512t-86d75fb0987f82f27ff03640e4e862970daa75db9498c932099196d80c51f0a33</citedby><cites>FETCH-LOGICAL-c512t-86d75fb0987f82f27ff03640e4e862970daa75db9498c932099196d80c51f0a33</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=996798$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11313881$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KALMA, Yael</creatorcontrib><creatorcontrib>MARASH, Lea</creatorcontrib><creatorcontrib>LAMED, Yocheved</creatorcontrib><creatorcontrib>GINSBERG, Doron</creatorcontrib><title>Expression analysis using DNA microarrays demonstrates that E2F-1 up-regulates expression of DNA replication genes including replication protein A2</title><title>Oncogene</title><addtitle>Oncogene</addtitle><description>The transcription factor E2F-1 plays a pivotal role in the regulation of G1/S transition in higher eukaryotes cell cycle. We used a cell line containing an inducible E2F-1 and oligonucleotide microarray analysis to identify novel E2F target genes. We show that E2F-1 up-regulates the expression of a number of genes coding for components of the DNA replication machinery. Among them is the gene coding for the 32 Kd subunit of replication protein A (RPA2). Replication protein A is the most abundant single strand DNA binding complex and it is essential for DNA replication. We demonstrate that RPA2 is a novel E2F target gene whose expression can be directly regulated by E2F-1 via E2F binding sites in its promoter. In addition, expression of Topoisomerase IIalpha and subunit IV of DNA polymerase alpha is also up-regulated upon E2F-1 induction. Taken together, these results provide novel links between components of the DNA replication machinery and the cell growth regulatory pathway involving the Rb tumor suppressor and E2F.</description><subject>Antigens, Neoplasm</subject><subject>Base Sequence</subject><subject>Binding sites</subject><subject>Biological and medical sciences</subject><subject>Carrier Proteins</subject><subject>Cell cycle</subject><subject>Cell Cycle Proteins</subject><subject>Cell cycle, cell proliferation</subject><subject>Cell growth</subject><subject>Cell physiology</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA biosynthesis</subject><subject>DNA microarrays</subject><subject>DNA polymerase</subject><subject>DNA Polymerase I - biosynthesis</subject><subject>DNA Replication - genetics</subject><subject>DNA Topoisomerases, Type II - biosynthesis</subject><subject>DNA-Binding Proteins - biosynthesis</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-directed DNA polymerase</subject><subject>E2F protein</subject><subject>E2F Transcription Factors</subject><subject>E2F-1 protein</subject><subject>E2F1 protein</subject><subject>E2F1 Transcription Factor</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Profiling</subject><subject>Genes</subject><subject>Humans</subject><subject>Isoenzymes - biosynthesis</subject><subject>Kinases</subject><subject>Molecular and cellular biology</subject><subject>Molecular Sequence Data</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Oligonucleotides</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Subunits</subject><subject>Proteins</subject><subject>RB protein</subject><subject>Replication Protein A</subject><subject>Retinoblastoma-Binding Protein 1</subject><subject>Transcription Factor DP1</subject><subject>Transcription Factors - metabolism</subject><subject>Tumor suppressor genes</subject><subject>Tumors</subject><subject>Up-Regulation</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFksGO0zAQhiMEYsvClSOKQOKWMrbj2D5WSxeQVnCBs-U6dnGV2MWTSNvn4IVxl4qu0CLkg6XxN_-MZ_6qeklgSYDJd7hbpmiXhEJLGTyqFqQVXcO5ah9XC1AcGkUZvaieIe4AQCigT6sLQhhhUpJF9XN9u88OMaRYm2iGAwasZwxxW7__vKrHYHMyOZsD1r0bU8Qpm8lhPX03U72m1w2p532T3XYe7uLuLJf8nUR2-yFYMx1DWxcLE6Id5v5Y4v7bPqfJhViv6PPqiTcDuhen-7L6dr3-evWxufny4dPV6qaxnNCpkV0vuN-AksJL6qnwHljXgmud7KgS0BsjeL9RrZJWMQpKEdX1Ekq6B8PYZfX2t24p_WN2OOkxoHXDYKJLM2ohQPBW8P-CREguhSQFfPMXuEtzLmNFTbu2DL0F0hXq9T8pKhhwKeVZamsGp0P0qUzeHuvqFQVgqmwTCrV8gCqnLCvYFJ0PJf5QQtkrYnZe73MYTT5oAvroKI07XRylT44qCa9Ozc6b0fVn_GShe382aM3gs4k24B9OqU4oyX4BltTSBw</recordid><startdate>20010315</startdate><enddate>20010315</enddate><creator>KALMA, Yael</creator><creator>MARASH, Lea</creator><creator>LAMED, Yocheved</creator><creator>GINSBERG, Doron</creator><general>Nature Publishing</general><general>Nature Publishing Group</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>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20010315</creationdate><title>Expression analysis using DNA microarrays demonstrates that E2F-1 up-regulates expression of DNA replication genes including replication protein A2</title><author>KALMA, Yael ; MARASH, Lea ; LAMED, Yocheved ; GINSBERG, Doron</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c512t-86d75fb0987f82f27ff03640e4e862970daa75db9498c932099196d80c51f0a33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Antigens, Neoplasm</topic><topic>Base Sequence</topic><topic>Binding sites</topic><topic>Biological and medical sciences</topic><topic>Carrier Proteins</topic><topic>Cell cycle</topic><topic>Cell Cycle Proteins</topic><topic>Cell cycle, cell proliferation</topic><topic>Cell growth</topic><topic>Cell physiology</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA biosynthesis</topic><topic>DNA microarrays</topic><topic>DNA polymerase</topic><topic>DNA Polymerase I - biosynthesis</topic><topic>DNA Replication - genetics</topic><topic>DNA Topoisomerases, Type II - biosynthesis</topic><topic>DNA-Binding Proteins - biosynthesis</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-directed DNA polymerase</topic><topic>E2F protein</topic><topic>E2F Transcription Factors</topic><topic>E2F-1 protein</topic><topic>E2F1 protein</topic><topic>E2F1 Transcription Factor</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Profiling</topic><topic>Genes</topic><topic>Humans</topic><topic>Isoenzymes - biosynthesis</topic><topic>Kinases</topic><topic>Molecular and cellular biology</topic><topic>Molecular Sequence Data</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Oligonucleotides</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Subunits</topic><topic>Proteins</topic><topic>RB protein</topic><topic>Replication Protein A</topic><topic>Retinoblastoma-Binding Protein 1</topic><topic>Transcription Factor DP1</topic><topic>Transcription Factors - metabolism</topic><topic>Tumor suppressor genes</topic><topic>Tumors</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KALMA, Yael</creatorcontrib><creatorcontrib>MARASH, Lea</creatorcontrib><creatorcontrib>LAMED, Yocheved</creatorcontrib><creatorcontrib>GINSBERG, Doron</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>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KALMA, Yael</au><au>MARASH, Lea</au><au>LAMED, Yocheved</au><au>GINSBERG, Doron</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression analysis using DNA microarrays demonstrates that E2F-1 up-regulates expression of DNA replication genes including replication protein A2</atitle><jtitle>Oncogene</jtitle><addtitle>Oncogene</addtitle><date>2001-03-15</date><risdate>2001</risdate><volume>20</volume><issue>11</issue><spage>1379</spage><epage>1387</epage><pages>1379-1387</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>The transcription factor E2F-1 plays a pivotal role in the regulation of G1/S transition in higher eukaryotes cell cycle. We used a cell line containing an inducible E2F-1 and oligonucleotide microarray analysis to identify novel E2F target genes. We show that E2F-1 up-regulates the expression of a number of genes coding for components of the DNA replication machinery. Among them is the gene coding for the 32 Kd subunit of replication protein A (RPA2). Replication protein A is the most abundant single strand DNA binding complex and it is essential for DNA replication. We demonstrate that RPA2 is a novel E2F target gene whose expression can be directly regulated by E2F-1 via E2F binding sites in its promoter. In addition, expression of Topoisomerase IIalpha and subunit IV of DNA polymerase alpha is also up-regulated upon E2F-1 induction. Taken together, these results provide novel links between components of the DNA replication machinery and the cell growth regulatory pathway involving the Rb tumor suppressor and E2F.</abstract><cop>Basingstoke</cop><pub>Nature Publishing</pub><pmid>11313881</pmid><doi>10.1038/sj.onc.1204230</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Antigens, Neoplasm Base Sequence Binding sites Biological and medical sciences Carrier Proteins Cell cycle Cell Cycle Proteins Cell cycle, cell proliferation Cell growth Cell physiology Deoxyribonucleic acid DNA DNA biosynthesis DNA microarrays DNA polymerase DNA Polymerase I - biosynthesis DNA Replication - genetics DNA Topoisomerases, Type II - biosynthesis DNA-Binding Proteins - biosynthesis DNA-Binding Proteins - genetics DNA-directed DNA polymerase E2F protein E2F Transcription Factors E2F-1 protein E2F1 protein E2F1 Transcription Factor Fundamental and applied biological sciences. Psychology Gene Expression Profiling Genes Humans Isoenzymes - biosynthesis Kinases Molecular and cellular biology Molecular Sequence Data Oligonucleotide Array Sequence Analysis Oligonucleotides Promoter Regions, Genetic Protein Subunits Proteins RB protein Replication Protein A Retinoblastoma-Binding Protein 1 Transcription Factor DP1 Transcription Factors - metabolism Tumor suppressor genes Tumors Up-Regulation |
title | Expression analysis using DNA microarrays demonstrates that E2F-1 up-regulates expression of DNA replication genes including replication protein A2 |
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