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bionlp-st-ge-2016-spacy-parsed

pmc-enju-pas

bionlp-st-ge-2016-coref

{"project":"bionlp-st-ge-2016-coref","denotations":[{"id":"T11520","span":{"begin":2065,"end":2076},"obj":"Antecedent"},{"id":"T11519","span":{"begin":2145,"end":2149},"obj":"Anaphor"},{"id":"T11518","span":{"begin":1971,"end":1976},"obj":"Antecedent"},{"id":"T11517","span":{"begin":2065,"end":2076},"obj":"Anaphor"}],"relations":[{"id":"R8507","pred":"boundBy","subj":"T11517","obj":"T11518"},{"id":"R8508","pred":"boundBy","subj":"T11519","obj":"T11517"}],"namespaces":[{"prefix":"_base","uri":"https://bionlp.dbcls.jp/ontology/ge.owl#"}],"text":"A C/EBP, CRE and Two AP-1 Sites in the Murine SerpinB2 Gene Proximal Promoter are Essential for Optimal LPS-inducible Transcription\nTo investigate regulatory elements between −539 and −189 essential for LPS-inducible transcription, several candidate binding sites for transcription factors previously reported to mediate LPS-inducible transcription in other genes [57] were targeted by nucleotide substitution designed to disrupt transcription factor binding to the pGLmP-539 murine SerpinB2 promoter-luciferase reporter gene construct (Fig. 4A). As shown in Fig. 4B, mutation of the consensus E box (−538/−533), PU.1 (−412/−407), or the variant Oct-1 (−296/−288) site did not decrease LPS-induced promoter activity. In contrast, mutation of the C/EBP site (−203/−192) completely eliminated promoter activity, similar to the levels observed for the −189 SerpinB2 promoter deletion construct. Others have also recently implicated this C/EBP site in LPS-induced activation of the SerpinB2 gene [58].\n10.1371/journal.pone.0057855.g004 Figure 4 Identification of cis-acting elements required for the LPS-responsiveness of the murine SerpinB2 promoter.\n(A) Schematic representation of the −539/+92 region of the murine SerpinB2 promoter with the location of candidate cis-acting regulatory elements indicated with boxes. The location of the 5′ ends of the −539, −189 and −87 reporter constructs is also shown. Positions of murine SerpinB2 proximal promoter-specific primers, 338/−315 and −5/+19 used in ChIP assays are indicated. (B) RAW 264.7 macrophages were transiently transfected with the indicated murine SerpinB2 promoter-luciferase reporter constructs and either left untreated or treated with 100 ng/ml LPS for 16 hrs. The results show relative luciferase activity following LPS treatment and represent the mean and SEM of 4–7 independent experiments. Considering the conserved sequence and position of the CRE and two AP-1 sites in the murine SerpinB2 promoter and their demonstrated involvement in the PMA-responsiveness of the human SERPINB2 promoter [37], these sites were also mutated by nucleotide substitution to investigate whether they played a role in the LPS response of the murine SerpinB2 promoter. As shown in Fig. 4B, mutation of the CRE at −177/−172 or either of the two AP-1 sites at −106/−100 and −94/−88, completely or significantly reduced LPS-inducible luciferase activity from the murine SerpinB2 promoter. These data show that the C/EBP element, as well as the CRE and both AP-1 cis-acting elements are critical for LPS-inducible transcription from the SerpinB2 proximal promoter."}

bionlp-st-ge-2016-test-proteins

{"project":"bionlp-st-ge-2016-test-proteins","denotations":[{"id":"T23799","span":{"begin":1750,"end":1760},"obj":"Protein"},{"id":"T23798","span":{"begin":1607,"end":1644},"obj":"Protein"},{"id":"T23797","span":{"begin":1426,"end":1434},"obj":"Protein"},{"id":"T23796","span":{"begin":1215,"end":1223},"obj":"Protein"},{"id":"T23795","span":{"begin":1130,"end":1138},"obj":"Protein"},{"id":"T11530","span":{"begin":2581,"end":2589},"obj":"Protein"},{"id":"T11529","span":{"begin":2415,"end":2423},"obj":"Protein"},{"id":"T11528","span":{"begin":2379,"end":2389},"obj":"Protein"},{"id":"T11527","span":{"begin":2198,"end":2206},"obj":"Protein"},{"id":"T11526","span":{"begin":2041,"end":2049},"obj":"Protein"},{"id":"T11525","span":{"begin":1949,"end":1957},"obj":"Protein"},{"id":"T11524","span":{"begin":978,"end":986},"obj":"Protein"},{"id":"T11523","span":{"begin":854,"end":862},"obj":"Protein"},{"id":"T11522","span":{"begin":483,"end":525},"obj":"Protein"},{"id":"T11521","span":{"begin":46,"end":54},"obj":"Protein"}],"namespaces":[{"prefix":"_base","uri":"http://bionlp.dbcls.jp/ontology/ge.owl#"}],"text":"A C/EBP, CRE and Two AP-1 Sites in the Murine SerpinB2 Gene Proximal Promoter are Essential for Optimal LPS-inducible Transcription\nTo investigate regulatory elements between −539 and −189 essential for LPS-inducible transcription, several candidate binding sites for transcription factors previously reported to mediate LPS-inducible transcription in other genes [57] were targeted by nucleotide substitution designed to disrupt transcription factor binding to the pGLmP-539 murine SerpinB2 promoter-luciferase reporter gene construct (Fig. 4A). As shown in Fig. 4B, mutation of the consensus E box (−538/−533), PU.1 (−412/−407), or the variant Oct-1 (−296/−288) site did not decrease LPS-induced promoter activity. In contrast, mutation of the C/EBP site (−203/−192) completely eliminated promoter activity, similar to the levels observed for the −189 SerpinB2 promoter deletion construct. Others have also recently implicated this C/EBP site in LPS-induced activation of the SerpinB2 gene [58].\n10.1371/journal.pone.0057855.g004 Figure 4 Identification of cis-acting elements required for the LPS-responsiveness of the murine SerpinB2 promoter.\n(A) Schematic representation of the −539/+92 region of the murine SerpinB2 promoter with the location of candidate cis-acting regulatory elements indicated with boxes. The location of the 5′ ends of the −539, −189 and −87 reporter constructs is also shown. Positions of murine SerpinB2 proximal promoter-specific primers, 338/−315 and −5/+19 used in ChIP assays are indicated. (B) RAW 264.7 macrophages were transiently transfected with the indicated murine SerpinB2 promoter-luciferase reporter constructs and either left untreated or treated with 100 ng/ml LPS for 16 hrs. The results show relative luciferase activity following LPS treatment and represent the mean and SEM of 4–7 independent experiments. Considering the conserved sequence and position of the CRE and two AP-1 sites in the murine SerpinB2 promoter and their demonstrated involvement in the PMA-responsiveness of the human SERPINB2 promoter [37], these sites were also mutated by nucleotide substitution to investigate whether they played a role in the LPS response of the murine SerpinB2 promoter. As shown in Fig. 4B, mutation of the CRE at −177/−172 or either of the two AP-1 sites at −106/−100 and −94/−88, completely or significantly reduced LPS-inducible luciferase activity from the murine SerpinB2 promoter. These data show that the C/EBP element, as well as the CRE and both AP-1 cis-acting elements are critical for LPS-inducible transcription from the SerpinB2 proximal promoter."}

bionlp-st-ge-2016-uniprot

GO-BP

{"project":"GO-BP","denotations":[{"id":"T23804","span":{"begin":1750,"end":1769},"obj":"http://purl.obolibrary.org/obo/GO_0050397"},{"id":"T23803","span":{"begin":1750,"end":1769},"obj":"http://purl.obolibrary.org/obo/GO_0050248"},{"id":"T23802","span":{"begin":1750,"end":1769},"obj":"http://purl.obolibrary.org/obo/GO_0047712"},{"id":"T23801","span":{"begin":1750,"end":1769},"obj":"http://purl.obolibrary.org/obo/GO_0047077"},{"id":"T23800","span":{"begin":1750,"end":1769},"obj":"http://purl.obolibrary.org/obo/GO_0045289"},{"id":"T11542","span":{"begin":2379,"end":2398},"obj":"http://purl.obolibrary.org/obo/GO_0050397"},{"id":"T11541","span":{"begin":2379,"end":2398},"obj":"http://purl.obolibrary.org/obo/GO_0050248"},{"id":"T11540","span":{"begin":2379,"end":2398},"obj":"http://purl.obolibrary.org/obo/GO_0047712"},{"id":"T11539","span":{"begin":2379,"end":2398},"obj":"http://purl.obolibrary.org/obo/GO_0047077"},{"id":"T11538","span":{"begin":2379,"end":2398},"obj":"http://purl.obolibrary.org/obo/GO_0045289"},{"id":"T11537","span":{"begin":2171,"end":2183},"obj":"http://purl.obolibrary.org/obo/GO_0032496"},{"id":"T11536","span":{"begin":2558,"end":2571},"obj":"http://purl.obolibrary.org/obo/GO_0006351"},{"id":"T11535","span":{"begin":430,"end":443},"obj":"http://purl.obolibrary.org/obo/GO_0006351"},{"id":"T11534","span":{"begin":335,"end":348},"obj":"http://purl.obolibrary.org/obo/GO_0006351"},{"id":"T11533","span":{"begin":268,"end":281},"obj":"http://purl.obolibrary.org/obo/GO_0006351"},{"id":"T11532","span":{"begin":217,"end":230},"obj":"http://purl.obolibrary.org/obo/GO_0006351"},{"id":"T11531","span":{"begin":118,"end":131},"obj":"http://purl.obolibrary.org/obo/GO_0006351"}],"text":"A C/EBP, CRE and Two AP-1 Sites in the Murine SerpinB2 Gene Proximal Promoter are Essential for Optimal LPS-inducible Transcription\nTo investigate regulatory elements between −539 and −189 essential for LPS-inducible transcription, several candidate binding sites for transcription factors previously reported to mediate LPS-inducible transcription in other genes [57] were targeted by nucleotide substitution designed to disrupt transcription factor binding to the pGLmP-539 murine SerpinB2 promoter-luciferase reporter gene construct (Fig. 4A). As shown in Fig. 4B, mutation of the consensus E box (−538/−533), PU.1 (−412/−407), or the variant Oct-1 (−296/−288) site did not decrease LPS-induced promoter activity. In contrast, mutation of the C/EBP site (−203/−192) completely eliminated promoter activity, similar to the levels observed for the −189 SerpinB2 promoter deletion construct. Others have also recently implicated this C/EBP site in LPS-induced activation of the SerpinB2 gene [58].\n10.1371/journal.pone.0057855.g004 Figure 4 Identification of cis-acting elements required for the LPS-responsiveness of the murine SerpinB2 promoter.\n(A) Schematic representation of the −539/+92 region of the murine SerpinB2 promoter with the location of candidate cis-acting regulatory elements indicated with boxes. The location of the 5′ ends of the −539, −189 and −87 reporter constructs is also shown. Positions of murine SerpinB2 proximal promoter-specific primers, 338/−315 and −5/+19 used in ChIP assays are indicated. (B) RAW 264.7 macrophages were transiently transfected with the indicated murine SerpinB2 promoter-luciferase reporter constructs and either left untreated or treated with 100 ng/ml LPS for 16 hrs. The results show relative luciferase activity following LPS treatment and represent the mean and SEM of 4–7 independent experiments. Considering the conserved sequence and position of the CRE and two AP-1 sites in the murine SerpinB2 promoter and their demonstrated involvement in the PMA-responsiveness of the human SERPINB2 promoter [37], these sites were also mutated by nucleotide substitution to investigate whether they played a role in the LPS response of the murine SerpinB2 promoter. As shown in Fig. 4B, mutation of the CRE at −177/−172 or either of the two AP-1 sites at −106/−100 and −94/−88, completely or significantly reduced LPS-inducible luciferase activity from the murine SerpinB2 promoter. These data show that the C/EBP element, as well as the CRE and both AP-1 cis-acting elements are critical for LPS-inducible transcription from the SerpinB2 proximal promoter."}

GO-MF

{"project":"GO-MF","denotations":[{"id":"T23809","span":{"begin":1750,"end":1769},"obj":"http://purl.obolibrary.org/obo/GO_0050397"},{"id":"T23808","span":{"begin":1750,"end":1769},"obj":"http://purl.obolibrary.org/obo/GO_0050248"},{"id":"T23807","span":{"begin":1750,"end":1769},"obj":"http://purl.obolibrary.org/obo/GO_0047712"},{"id":"T23806","span":{"begin":1750,"end":1769},"obj":"http://purl.obolibrary.org/obo/GO_0047077"},{"id":"T23805","span":{"begin":1750,"end":1769},"obj":"http://purl.obolibrary.org/obo/GO_0045289"},{"id":"T11553","span":{"begin":2379,"end":2398},"obj":"http://purl.obolibrary.org/obo/GO_0050397"},{"id":"T11552","span":{"begin":2379,"end":2398},"obj":"http://purl.obolibrary.org/obo/GO_0050248"},{"id":"T11551","span":{"begin":2379,"end":2398},"obj":"http://purl.obolibrary.org/obo/GO_0047712"},{"id":"T11550","span":{"begin":2379,"end":2398},"obj":"http://purl.obolibrary.org/obo/GO_0047077"},{"id":"T11549","span":{"begin":2379,"end":2398},"obj":"http://purl.obolibrary.org/obo/GO_0045289"},{"id":"T11548","span":{"begin":430,"end":458},"obj":"http://purl.obolibrary.org/obo/GO_0070491"},{"id":"T11547","span":{"begin":430,"end":458},"obj":"http://purl.obolibrary.org/obo/GO_0043425"},{"id":"T11546","span":{"begin":430,"end":458},"obj":"http://purl.obolibrary.org/obo/GO_0033613"},{"id":"T11545","span":{"begin":430,"end":458},"obj":"http://purl.obolibrary.org/obo/GO_0008134"},{"id":"T11544","span":{"begin":451,"end":458},"obj":"http://purl.obolibrary.org/obo/GO_0005488"},{"id":"T11543","span":{"begin":250,"end":257},"obj":"http://purl.obolibrary.org/obo/GO_0005488"}],"text":"A C/EBP, CRE and Two AP-1 Sites in the Murine SerpinB2 Gene Proximal Promoter are Essential for Optimal LPS-inducible Transcription\nTo investigate regulatory elements between −539 and −189 essential for LPS-inducible transcription, several candidate binding sites for transcription factors previously reported to mediate LPS-inducible transcription in other genes [57] were targeted by nucleotide substitution designed to disrupt transcription factor binding to the pGLmP-539 murine SerpinB2 promoter-luciferase reporter gene construct (Fig. 4A). As shown in Fig. 4B, mutation of the consensus E box (−538/−533), PU.1 (−412/−407), or the variant Oct-1 (−296/−288) site did not decrease LPS-induced promoter activity. In contrast, mutation of the C/EBP site (−203/−192) completely eliminated promoter activity, similar to the levels observed for the −189 SerpinB2 promoter deletion construct. Others have also recently implicated this C/EBP site in LPS-induced activation of the SerpinB2 gene [58].\n10.1371/journal.pone.0057855.g004 Figure 4 Identification of cis-acting elements required for the LPS-responsiveness of the murine SerpinB2 promoter.\n(A) Schematic representation of the −539/+92 region of the murine SerpinB2 promoter with the location of candidate cis-acting regulatory elements indicated with boxes. The location of the 5′ ends of the −539, −189 and −87 reporter constructs is also shown. Positions of murine SerpinB2 proximal promoter-specific primers, 338/−315 and −5/+19 used in ChIP assays are indicated. (B) RAW 264.7 macrophages were transiently transfected with the indicated murine SerpinB2 promoter-luciferase reporter constructs and either left untreated or treated with 100 ng/ml LPS for 16 hrs. The results show relative luciferase activity following LPS treatment and represent the mean and SEM of 4–7 independent experiments. Considering the conserved sequence and position of the CRE and two AP-1 sites in the murine SerpinB2 promoter and their demonstrated involvement in the PMA-responsiveness of the human SERPINB2 promoter [37], these sites were also mutated by nucleotide substitution to investigate whether they played a role in the LPS response of the murine SerpinB2 promoter. As shown in Fig. 4B, mutation of the CRE at −177/−172 or either of the two AP-1 sites at −106/−100 and −94/−88, completely or significantly reduced LPS-inducible luciferase activity from the murine SerpinB2 promoter. These data show that the C/EBP element, as well as the CRE and both AP-1 cis-acting elements are critical for LPS-inducible transcription from the SerpinB2 proximal promoter."}

sentences

simple1

{"project":"simple1","denotations":[{"id":"T23814","span":{"begin":1750,"end":1760},"obj":"Protein"},{"id":"T23813","span":{"begin":1607,"end":1644},"obj":"Protein"},{"id":"T23812","span":{"begin":1426,"end":1434},"obj":"Protein"},{"id":"T23811","span":{"begin":1215,"end":1223},"obj":"Protein"},{"id":"T23810","span":{"begin":1130,"end":1138},"obj":"Protein"},{"id":"T11554","span":{"begin":46,"end":54},"obj":"Protein"},{"id":"T11563","span":{"begin":2581,"end":2589},"obj":"Protein"},{"id":"T11562","span":{"begin":2415,"end":2423},"obj":"Protein"},{"id":"T11561","span":{"begin":2379,"end":2389},"obj":"Protein"},{"id":"T11560","span":{"begin":2198,"end":2206},"obj":"Protein"},{"id":"T11559","span":{"begin":2041,"end":2049},"obj":"Protein"},{"id":"T11558","span":{"begin":1949,"end":1957},"obj":"Protein"},{"id":"T11557","span":{"begin":978,"end":986},"obj":"Protein"},{"id":"T11556","span":{"begin":854,"end":862},"obj":"Protein"},{"id":"T11555","span":{"begin":483,"end":525},"obj":"Protein"}],"text":"A C/EBP, CRE and Two AP-1 Sites in the Murine SerpinB2 Gene Proximal Promoter are Essential for Optimal LPS-inducible Transcription\nTo investigate regulatory elements between −539 and −189 essential for LPS-inducible transcription, several candidate binding sites for transcription factors previously reported to mediate LPS-inducible transcription in other genes [57] were targeted by nucleotide substitution designed to disrupt transcription factor binding to the pGLmP-539 murine SerpinB2 promoter-luciferase reporter gene construct (Fig. 4A). As shown in Fig. 4B, mutation of the consensus E box (−538/−533), PU.1 (−412/−407), or the variant Oct-1 (−296/−288) site did not decrease LPS-induced promoter activity. In contrast, mutation of the C/EBP site (−203/−192) completely eliminated promoter activity, similar to the levels observed for the −189 SerpinB2 promoter deletion construct. Others have also recently implicated this C/EBP site in LPS-induced activation of the SerpinB2 gene [58].\n10.1371/journal.pone.0057855.g004 Figure 4 Identification of cis-acting elements required for the LPS-responsiveness of the murine SerpinB2 promoter.\n(A) Schematic representation of the −539/+92 region of the murine SerpinB2 promoter with the location of candidate cis-acting regulatory elements indicated with boxes. The location of the 5′ ends of the −539, −189 and −87 reporter constructs is also shown. Positions of murine SerpinB2 proximal promoter-specific primers, 338/−315 and −5/+19 used in ChIP assays are indicated. (B) RAW 264.7 macrophages were transiently transfected with the indicated murine SerpinB2 promoter-luciferase reporter constructs and either left untreated or treated with 100 ng/ml LPS for 16 hrs. The results show relative luciferase activity following LPS treatment and represent the mean and SEM of 4–7 independent experiments. Considering the conserved sequence and position of the CRE and two AP-1 sites in the murine SerpinB2 promoter and their demonstrated involvement in the PMA-responsiveness of the human SERPINB2 promoter [37], these sites were also mutated by nucleotide substitution to investigate whether they played a role in the LPS response of the murine SerpinB2 promoter. As shown in Fig. 4B, mutation of the CRE at −177/−172 or either of the two AP-1 sites at −106/−100 and −94/−88, completely or significantly reduced LPS-inducible luciferase activity from the murine SerpinB2 promoter. These data show that the C/EBP element, as well as the CRE and both AP-1 cis-acting elements are critical for LPS-inducible transcription from the SerpinB2 proximal promoter."}

BioNLP16_DUT

BioNLP16_Messiy

{"project":"BioNLP16_Messiy","denotations":[{"id":"T11930","span":{"begin":2357,"end":2364},"obj":"Negative_regulation"},{"id":"T11929","span":{"begin":960,"end":970},"obj":"Positive_regulation"},{"id":"T11928","span":{"begin":451,"end":458},"obj":"Binding"},{"id":"T11927","span":{"begin":2581,"end":2589},"obj":"Protein"},{"id":"T11926","span":{"begin":2415,"end":2423},"obj":"Protein"},{"id":"T11925","span":{"begin":2379,"end":2389},"obj":"Protein"},{"id":"T11924","span":{"begin":2198,"end":2206},"obj":"Protein"},{"id":"T11923","span":{"begin":2041,"end":2049},"obj":"Protein"},{"id":"T11922","span":{"begin":1949,"end":1957},"obj":"Protein"},{"id":"T11921","span":{"begin":978,"end":986},"obj":"Protein"},{"id":"T11920","span":{"begin":854,"end":862},"obj":"Protein"},{"id":"T11919","span":{"begin":483,"end":525},"obj":"Protein"},{"id":"T11918","span":{"begin":46,"end":54},"obj":"Protein"},{"id":"T23970","span":{"begin":1569,"end":1580},"obj":"Gene_expression"},{"id":"T23969","span":{"begin":1750,"end":1760},"obj":"Protein"},{"id":"T23968","span":{"begin":1607,"end":1644},"obj":"Protein"},{"id":"T23967","span":{"begin":1426,"end":1434},"obj":"Protein"},{"id":"T23966","span":{"begin":1215,"end":1223},"obj":"Protein"},{"id":"T23965","span":{"begin":1130,"end":1138},"obj":"Protein"}],"relations":[{"id":"R8816","pred":"themeOf","subj":"T11919","obj":"T11928"},{"id":"R8817","pred":"themeOf","subj":"T11921","obj":"T11929"},{"id":"R8818","pred":"themeOf","subj":"T11925","obj":"T11930"},{"id":"R17237","pred":"themeOf","subj":"T23968","obj":"T23970"}],"text":"A C/EBP, CRE and Two AP-1 Sites in the Murine SerpinB2 Gene Proximal Promoter are Essential for Optimal LPS-inducible Transcription\nTo investigate regulatory elements between −539 and −189 essential for LPS-inducible transcription, several candidate binding sites for transcription factors previously reported to mediate LPS-inducible transcription in other genes [57] were targeted by nucleotide substitution designed to disrupt transcription factor binding to the pGLmP-539 murine SerpinB2 promoter-luciferase reporter gene construct (Fig. 4A). As shown in Fig. 4B, mutation of the consensus E box (−538/−533), PU.1 (−412/−407), or the variant Oct-1 (−296/−288) site did not decrease LPS-induced promoter activity. In contrast, mutation of the C/EBP site (−203/−192) completely eliminated promoter activity, similar to the levels observed for the −189 SerpinB2 promoter deletion construct. Others have also recently implicated this C/EBP site in LPS-induced activation of the SerpinB2 gene [58].\n10.1371/journal.pone.0057855.g004 Figure 4 Identification of cis-acting elements required for the LPS-responsiveness of the murine SerpinB2 promoter.\n(A) Schematic representation of the −539/+92 region of the murine SerpinB2 promoter with the location of candidate cis-acting regulatory elements indicated with boxes. The location of the 5′ ends of the −539, −189 and −87 reporter constructs is also shown. Positions of murine SerpinB2 proximal promoter-specific primers, 338/−315 and −5/+19 used in ChIP assays are indicated. (B) RAW 264.7 macrophages were transiently transfected with the indicated murine SerpinB2 promoter-luciferase reporter constructs and either left untreated or treated with 100 ng/ml LPS for 16 hrs. The results show relative luciferase activity following LPS treatment and represent the mean and SEM of 4–7 independent experiments. Considering the conserved sequence and position of the CRE and two AP-1 sites in the murine SerpinB2 promoter and their demonstrated involvement in the PMA-responsiveness of the human SERPINB2 promoter [37], these sites were also mutated by nucleotide substitution to investigate whether they played a role in the LPS response of the murine SerpinB2 promoter. As shown in Fig. 4B, mutation of the CRE at −177/−172 or either of the two AP-1 sites at −106/−100 and −94/−88, completely or significantly reduced LPS-inducible luciferase activity from the murine SerpinB2 promoter. These data show that the C/EBP element, as well as the CRE and both AP-1 cis-acting elements are critical for LPS-inducible transcription from the SerpinB2 proximal promoter."}

DLUT931

bionlp-st-ge-2016-test-ihmc

bionlp-st-ge-2016-test-tees

testone

{"project":"testone","denotations":[{"id":"T23769","span":{"begin":1750,"end":1760},"obj":"Protein"},{"id":"T23768","span":{"begin":1607,"end":1644},"obj":"Protein"},{"id":"T23767","span":{"begin":1426,"end":1434},"obj":"Protein"},{"id":"T23766","span":{"begin":1215,"end":1223},"obj":"Protein"},{"id":"T23765","span":{"begin":1130,"end":1138},"obj":"Protein"},{"id":"T11416","span":{"begin":2369,"end":2378},"obj":"Positive_regulation"},{"id":"T11415","span":{"begin":2357,"end":2364},"obj":"Negative_regulation"},{"id":"T11414","span":{"begin":952,"end":959},"obj":"Positive_regulation"},{"id":"T11413","span":{"begin":752,"end":756},"obj":"Entity"},{"id":"T11412","span":{"begin":451,"end":458},"obj":"Binding"},{"id":"T11411","span":{"begin":2581,"end":2589},"obj":"Protein"},{"id":"T11410","span":{"begin":2415,"end":2423},"obj":"Protein"},{"id":"T11409","span":{"begin":2379,"end":2389},"obj":"Protein"},{"id":"T11408","span":{"begin":2198,"end":2206},"obj":"Protein"},{"id":"T11407","span":{"begin":2041,"end":2049},"obj":"Protein"},{"id":"T11406","span":{"begin":1949,"end":1957},"obj":"Protein"},{"id":"T11405","span":{"begin":978,"end":986},"obj":"Protein"},{"id":"T11404","span":{"begin":854,"end":862},"obj":"Protein"},{"id":"T11403","span":{"begin":483,"end":525},"obj":"Protein"},{"id":"T11402","span":{"begin":46,"end":54},"obj":"Protein"}],"relations":[{"id":"R8428","pred":"themeOf","subj":"T11403","obj":"T11412"},{"id":"R8429","pred":"themeOf","subj":"T11409","obj":"T11416"},{"id":"R8430","pred":"themeOf","subj":"T11416","obj":"T11415"}],"text":"A C/EBP, CRE and Two AP-1 Sites in the Murine SerpinB2 Gene Proximal Promoter are Essential for Optimal LPS-inducible Transcription\nTo investigate regulatory elements between −539 and −189 essential for LPS-inducible transcription, several candidate binding sites for transcription factors previously reported to mediate LPS-inducible transcription in other genes [57] were targeted by nucleotide substitution designed to disrupt transcription factor binding to the pGLmP-539 murine SerpinB2 promoter-luciferase reporter gene construct (Fig. 4A). As shown in Fig. 4B, mutation of the consensus E box (−538/−533), PU.1 (−412/−407), or the variant Oct-1 (−296/−288) site did not decrease LPS-induced promoter activity. In contrast, mutation of the C/EBP site (−203/−192) completely eliminated promoter activity, similar to the levels observed for the −189 SerpinB2 promoter deletion construct. Others have also recently implicated this C/EBP site in LPS-induced activation of the SerpinB2 gene [58].\n10.1371/journal.pone.0057855.g004 Figure 4 Identification of cis-acting elements required for the LPS-responsiveness of the murine SerpinB2 promoter.\n(A) Schematic representation of the −539/+92 region of the murine SerpinB2 promoter with the location of candidate cis-acting regulatory elements indicated with boxes. The location of the 5′ ends of the −539, −189 and −87 reporter constructs is also shown. Positions of murine SerpinB2 proximal promoter-specific primers, 338/−315 and −5/+19 used in ChIP assays are indicated. (B) RAW 264.7 macrophages were transiently transfected with the indicated murine SerpinB2 promoter-luciferase reporter constructs and either left untreated or treated with 100 ng/ml LPS for 16 hrs. The results show relative luciferase activity following LPS treatment and represent the mean and SEM of 4–7 independent experiments. Considering the conserved sequence and position of the CRE and two AP-1 sites in the murine SerpinB2 promoter and their demonstrated involvement in the PMA-responsiveness of the human SERPINB2 promoter [37], these sites were also mutated by nucleotide substitution to investigate whether they played a role in the LPS response of the murine SerpinB2 promoter. As shown in Fig. 4B, mutation of the CRE at −177/−172 or either of the two AP-1 sites at −106/−100 and −94/−88, completely or significantly reduced LPS-inducible luciferase activity from the murine SerpinB2 promoter. These data show that the C/EBP element, as well as the CRE and both AP-1 cis-acting elements are critical for LPS-inducible transcription from the SerpinB2 proximal promoter."}

test3

PMC:3589482 / 24557-27165 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:3589482 / 24557-27165 JSON TXT