Ras/MAPK Signaling Modulates VEGFR-3 Expression through Ets-Mediated p300 Recruitment and Histone Acetylation on the Vegfr3 Gene in Lymphatic Endothelial Cells
Identifieur interne : 002761 ( Pmc/Checkpoint ); précédent : 002760; suivant : 002762Ras/MAPK Signaling Modulates VEGFR-3 Expression through Ets-Mediated p300 Recruitment and Histone Acetylation on the Vegfr3 Gene in Lymphatic Endothelial Cells
Auteurs : Taeko Ichise ; Nobuaki Yoshida ; Hirotake IchiseSource :
- PLoS ONE [ 1932-6203 ] ; 2012.
Abstract
Modulation of VEGFR-3 expression is important for altering lymphatic endothelial cell (LEC) characteristics during the lymphangiogenic processes that occur under developmental, physiological, and pathological conditions. However, the mechanisms underlying the modulation of
Url:
DOI: 10.1371/journal.pone.0051639
PubMed: 23284731
PubMed Central: 3524184
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
PMC:3524184Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Ras/MAPK Signaling Modulates VEGFR-3 Expression through Ets-Mediated p300 Recruitment and Histone Acetylation on the <italic>Vegfr3</italic> Gene in Lymphatic Endothelial Cells</title><author><name sortKey="Ichise, Taeko" sort="Ichise, Taeko" uniqKey="Ichise T" first="Taeko" last="Ichise">Taeko Ichise</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Yoshida, Nobuaki" sort="Yoshida, Nobuaki" uniqKey="Yoshida N" first="Nobuaki" last="Yoshida">Nobuaki Yoshida</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Ichise, Hirotake" sort="Ichise, Hirotake" uniqKey="Ichise H" first="Hirotake" last="Ichise">Hirotake Ichise</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23284731</idno><idno type="pmc">3524184</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524184</idno><idno type="RBID">PMC:3524184</idno><idno type="doi">10.1371/journal.pone.0051639</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">004461</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">004461</idno><idno type="wicri:Area/Pmc/Curation">004460</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">004460</idno><idno type="wicri:Area/Pmc/Checkpoint">002761</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">002761</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Ras/MAPK Signaling Modulates VEGFR-3 Expression through Ets-Mediated p300 Recruitment and Histone Acetylation on the <italic>Vegfr3</italic> Gene in Lymphatic Endothelial Cells</title><author><name sortKey="Ichise, Taeko" sort="Ichise, Taeko" uniqKey="Ichise T" first="Taeko" last="Ichise">Taeko Ichise</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Yoshida, Nobuaki" sort="Yoshida, Nobuaki" uniqKey="Yoshida N" first="Nobuaki" last="Yoshida">Nobuaki Yoshida</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Ichise, Hirotake" sort="Ichise, Hirotake" uniqKey="Ichise H" first="Hirotake" last="Ichise">Hirotake Ichise</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Modulation of VEGFR-3 expression is important for altering lymphatic endothelial cell (LEC) characteristics during the lymphangiogenic processes that occur under developmental, physiological, and pathological conditions. However, the mechanisms underlying the modulation of <italic>Vegfr3</italic> gene expression remain largely unknown. Using genetically engineered mice and LECs, we demonstrated previously that Ras signaling is involved not only in VEGFR-3-induced signal transduction but also in <italic>Vegfr3</italic> gene expression. Here, we investigated the roles of the transcription factor Ets and the histone acetyltransferase p300 in LECs in Ras-mediated transcriptional regulation of <italic>Vegfr3</italic>. Ras activates Ets proteins via MAPK-induced phosphorylation. Ets knockdown, similar to Ras knockdown, resulted in a decrease in both <italic>Vegfr3</italic> transcript levels and acetylated histone H3 on the <italic>Vegfr3</italic> gene. <italic>Vegfr3</italic> knockdown results in altered LEC phenotypes, such as aberrant cell proliferation and network formation, and Ets knockdown led to milder but similar phenotypic changes. We identified evolutionarily conserved, non-coding regulatory elements within the <italic>Vegfr3</italic> gene that harbor Ets-binding motifs and have enhancer activities in LECs. Chromatin immunoprecipitation (ChIP) assays revealed that acetylated histone H3 on the regulatory elements of the <italic>Vegfr3</italic> gene was decreased following Ras and Ets knockdown, and that activated Ets proteins, together with p300, were associated with these regulatory elements, consistent with a reduction in <italic>Vegfr3</italic> gene expression in p300-knockdown LECs. Our findings demonstrate a link between Ras signaling and Ets- and p300-mediated transcriptional regulation of <italic>Vegfr3</italic>, and provide a potential mechanism by which VEGFR-3 expression levels may be modulated during lymphangiogenesis.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Alitalo, K" uniqKey="Alitalo K">K Alitalo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Karkkainen, Mj" uniqKey="Karkkainen M">MJ Karkkainen</name></author><author><name sortKey="Ferrell, Re" uniqKey="Ferrell R">RE Ferrell</name></author><author><name sortKey="Lawrence, Ec" uniqKey="Lawrence E">EC Lawrence</name></author><author><name sortKey="Kimak, Ma" uniqKey="Kimak M">MA Kimak</name></author><author><name sortKey="Levinson, Kl" uniqKey="Levinson K">KL Levinson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Karkkainen, Mj" uniqKey="Karkkainen M">MJ Karkkainen</name></author><author><name sortKey="Saaristo, A" uniqKey="Saaristo A">A Saaristo</name></author><author><name sortKey="Jussila, L" uniqKey="Jussila L">L Jussila</name></author><author><name sortKey="Karila, Ka" uniqKey="Karila K">KA Karila</name></author><author><name sortKey="Lawrence, Ec" uniqKey="Lawrence E">EC Lawrence</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haiko, P" uniqKey="Haiko P">P Haiko</name></author><author><name sortKey="Makinen, T" uniqKey="Makinen T">T Makinen</name></author><author><name sortKey="Keskitalo, S" uniqKey="Keskitalo S">S Keskitalo</name></author><author><name sortKey="Taipale, J" uniqKey="Taipale J">J Taipale</name></author><author><name sortKey="Karkkainen, Mj" uniqKey="Karkkainen M">MJ Karkkainen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, L" uniqKey="Zhang L">L Zhang</name></author><author><name sortKey="Zhou, F" uniqKey="Zhou F">F Zhou</name></author><author><name sortKey="Han, W" uniqKey="Han W">W Han</name></author><author><name sortKey="Shen, B" uniqKey="Shen B">B Shen</name></author><author><name sortKey="Luo, J" uniqKey="Luo J">J Luo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dumont, Dj" uniqKey="Dumont D">DJ Dumont</name></author><author><name sortKey="Jussila, L" uniqKey="Jussila L">L Jussila</name></author><author><name sortKey="Taipale, J" uniqKey="Taipale J">J Taipale</name></author><author><name sortKey="Lymboussaki, A" uniqKey="Lymboussaki A">A Lymboussaki</name></author><author><name sortKey="Mustonen, T" uniqKey="Mustonen T">T Mustonen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Karkkainen, Mj" uniqKey="Karkkainen M">MJ Karkkainen</name></author><author><name sortKey="Haiko, P" uniqKey="Haiko P">P Haiko</name></author><author><name sortKey="Sainio, K" uniqKey="Sainio K">K Sainio</name></author><author><name sortKey="Partanen, J" uniqKey="Partanen J">J Partanen</name></author><author><name sortKey="Taipale, J" uniqKey="Taipale J">J Taipale</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="He, Y" uniqKey="He Y">Y He</name></author><author><name sortKey="Kozaki, K" uniqKey="Kozaki K">K Kozaki</name></author><author><name sortKey="Karpanen, T" uniqKey="Karpanen T">T Karpanen</name></author><author><name sortKey="Koshikawa, K" uniqKey="Koshikawa K">K Koshikawa</name></author><author><name sortKey="Yla Herttuala, S" uniqKey="Yla Herttuala S">S Yla-Herttuala</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pytowski, B" uniqKey="Pytowski B">B Pytowski</name></author><author><name sortKey="Goldman, J" uniqKey="Goldman J">J Goldman</name></author><author><name sortKey="Persaud, K" uniqKey="Persaud K">K Persaud</name></author><author><name sortKey="Wu, Y" uniqKey="Wu Y">Y Wu</name></author><author><name sortKey="Witte, L" uniqKey="Witte L">L Witte</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baluk, P" uniqKey="Baluk P">P Baluk</name></author><author><name sortKey="Tammela, T" uniqKey="Tammela T">T Tammela</name></author><author><name sortKey="Ator, E" uniqKey="Ator E">E Ator</name></author><author><name sortKey="Lyubynska, N" uniqKey="Lyubynska N">N Lyubynska</name></author><author><name sortKey="Achen, Mg" uniqKey="Achen M">MG Achen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Flister, Mj" uniqKey="Flister M">MJ Flister</name></author><author><name sortKey="Wilber, A" uniqKey="Wilber A">A Wilber</name></author><author><name sortKey="Hall, Kl" uniqKey="Hall K">KL Hall</name></author><author><name sortKey="Iwata, C" uniqKey="Iwata C">C Iwata</name></author><author><name sortKey="Miyazono, K" uniqKey="Miyazono K">K Miyazono</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huggenberger, R" uniqKey="Huggenberger R">R Huggenberger</name></author><author><name sortKey="Siddiqui, Ss" uniqKey="Siddiqui S">SS Siddiqui</name></author><author><name sortKey="Brander, D" uniqKey="Brander D">D Brander</name></author><author><name sortKey="Ullmann, S" uniqKey="Ullmann S">S Ullmann</name></author><author><name sortKey="Zimmermann, K" uniqKey="Zimmermann K">K Zimmermann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yoshimatsu, Y" uniqKey="Yoshimatsu Y">Y Yoshimatsu</name></author><author><name sortKey="Yamazaki, T" uniqKey="Yamazaki T">T Yamazaki</name></author><author><name sortKey="Mihira, H" uniqKey="Mihira H">H Mihira</name></author><author><name sortKey="Itoh, T" uniqKey="Itoh T">T Itoh</name></author><author><name sortKey="Suehiro, J" uniqKey="Suehiro J">J Suehiro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jones, D" uniqKey="Jones D">D Jones</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author><author><name sortKey="He, Y" uniqKey="He Y">Y He</name></author><author><name sortKey="Xu, Z" uniqKey="Xu Z">Z Xu</name></author><author><name sortKey="Chen, H" uniqKey="Chen H">H Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, Hy" uniqKey="Huang H">HY Huang</name></author><author><name sortKey="Ho, Cc" uniqKey="Ho C">CC Ho</name></author><author><name sortKey="Huang, Ph" uniqKey="Huang P">PH Huang</name></author><author><name sortKey="Hsu, Sm" uniqKey="Hsu S">SM Hsu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hong, Yk" uniqKey="Hong Y">YK Hong</name></author><author><name sortKey="Foreman, K" uniqKey="Foreman K">K Foreman</name></author><author><name sortKey="Shin, Jw" uniqKey="Shin J">JW Shin</name></author><author><name sortKey="Hirakawa, S" uniqKey="Hirakawa S">S Hirakawa</name></author><author><name sortKey="Curry, Cl" uniqKey="Curry C">CL Curry</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Hw" uniqKey="Wang H">HW Wang</name></author><author><name sortKey="Trotter, Mw" uniqKey="Trotter M">MW Trotter</name></author><author><name sortKey="Lagos, D" uniqKey="Lagos D">D Lagos</name></author><author><name sortKey="Bourboulia, D" uniqKey="Bourboulia D">D Bourboulia</name></author><author><name sortKey="Henderson, S" uniqKey="Henderson S">S Henderson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Iljin, K" uniqKey="Iljin K">K Iljin</name></author><author><name sortKey="Karkkainen, Mj" uniqKey="Karkkainen M">MJ Karkkainen</name></author><author><name sortKey="Lawrence, Ec" uniqKey="Lawrence E">EC Lawrence</name></author><author><name sortKey="Kimak, Ma" uniqKey="Kimak M">MA Kimak</name></author><author><name sortKey="Uutela, M" uniqKey="Uutela M">M Uutela</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shawber, Cj" uniqKey="Shawber C">CJ Shawber</name></author><author><name sortKey="Funahashi, Y" uniqKey="Funahashi Y">Y Funahashi</name></author><author><name sortKey="Francisco, E" uniqKey="Francisco E">E Francisco</name></author><author><name sortKey="Vorontchikhina, M" uniqKey="Vorontchikhina M">M Vorontchikhina</name></author><author><name sortKey="Kitamura, Y" uniqKey="Kitamura Y">Y Kitamura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hong, Yk" uniqKey="Hong Y">YK Hong</name></author><author><name sortKey="Harvey, N" uniqKey="Harvey N">N Harvey</name></author><author><name sortKey="Noh, Yh" uniqKey="Noh Y">YH Noh</name></author><author><name sortKey="Schacht, V" uniqKey="Schacht V">V Schacht</name></author><author><name sortKey="Hirakawa, S" uniqKey="Hirakawa S">S Hirakawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Petrova, Tv" uniqKey="Petrova T">TV Petrova</name></author><author><name sortKey="Makinen, T" uniqKey="Makinen T">T Makinen</name></author><author><name sortKey="Makela, Tp" uniqKey="Makela T">TP Makela</name></author><author><name sortKey="Saarela, J" uniqKey="Saarela J">J Saarela</name></author><author><name sortKey="Virtanen, I" uniqKey="Virtanen I">I Virtanen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mishima, K" uniqKey="Mishima K">K Mishima</name></author><author><name sortKey="Watabe, T" uniqKey="Watabe T">T Watabe</name></author><author><name sortKey="Saito, A" uniqKey="Saito A">A Saito</name></author><author><name sortKey="Yoshimatsu, Y" uniqKey="Yoshimatsu Y">Y Yoshimatsu</name></author><author><name sortKey="Imaizumi, N" uniqKey="Imaizumi N">N Imaizumi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pan, Mr" uniqKey="Pan M">MR Pan</name></author><author><name sortKey="Chang, Tm" uniqKey="Chang T">TM Chang</name></author><author><name sortKey="Chang, Hc" uniqKey="Chang H">HC Chang</name></author><author><name sortKey="Su, Jl" uniqKey="Su J">JL Su</name></author><author><name sortKey="Wang, Hw" uniqKey="Wang H">HW Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, S" uniqKey="Lee S">S Lee</name></author><author><name sortKey="Kang, J" uniqKey="Kang J">J Kang</name></author><author><name sortKey="Yoo, J" uniqKey="Yoo J">J Yoo</name></author><author><name sortKey="Ganesan, Sk" uniqKey="Ganesan S">SK Ganesan</name></author><author><name sortKey="Cook, Sc" uniqKey="Cook S">SC Cook</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, L" uniqKey="Chen L">L Chen</name></author><author><name sortKey="Mupo, A" uniqKey="Mupo A">A Mupo</name></author><author><name sortKey="Huynh, T" uniqKey="Huynh T">T Huynh</name></author><author><name sortKey="Cioffi, S" uniqKey="Cioffi S">S Cioffi</name></author><author><name sortKey="Woods, M" uniqKey="Woods M">M Woods</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ichise, T" uniqKey="Ichise T">T Ichise</name></author><author><name sortKey="Yoshida, N" uniqKey="Yoshida N">N Yoshida</name></author><author><name sortKey="Ichise, H" uniqKey="Ichise H">H Ichise</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hollenhorst, Pc" uniqKey="Hollenhorst P">PC Hollenhorst</name></author><author><name sortKey="Mcintosh, Lp" uniqKey="Mcintosh L">LP McIntosh</name></author><author><name sortKey="Graves, Bj" uniqKey="Graves B">BJ Graves</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brunner, D" uniqKey="Brunner D">D Brunner</name></author><author><name sortKey="Ducker, K" uniqKey="Ducker K">K Ducker</name></author><author><name sortKey="Oellers, N" uniqKey="Oellers N">N Oellers</name></author><author><name sortKey="Hafen, E" uniqKey="Hafen E">E Hafen</name></author><author><name sortKey="Scholz, H" uniqKey="Scholz H">H Scholz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="O Eill, Em" uniqKey="O Eill E">EM O’Neill</name></author><author><name sortKey="Rebay, I" uniqKey="Rebay I">I Rebay</name></author><author><name sortKey="Tjian, R" uniqKey="Tjian R">R Tjian</name></author><author><name sortKey="Rubin, Gm" uniqKey="Rubin G">GM Rubin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Bs" uniqKey="Yang B">BS Yang</name></author><author><name sortKey="Hauser, Ca" uniqKey="Hauser C">CA Hauser</name></author><author><name sortKey="Henkel, G" uniqKey="Henkel G">G Henkel</name></author><author><name sortKey="Colman, Ms" uniqKey="Colman M">MS Colman</name></author><author><name sortKey="Van Beveren, C" uniqKey="Van Beveren C">C Van Beveren</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wasylyk, C" uniqKey="Wasylyk C">C Wasylyk</name></author><author><name sortKey="Bradford, Ap" uniqKey="Bradford A">AP Bradford</name></author><author><name sortKey="Gutierrez Hartmann, A" uniqKey="Gutierrez Hartmann A">A Gutierrez-Hartmann</name></author><author><name sortKey="Wasylyk, B" uniqKey="Wasylyk B">B Wasylyk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Val, S" uniqKey="De Val S">S De Val</name></author><author><name sortKey="Black, Bl" uniqKey="Black B">BL Black</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Meadows, Sm" uniqKey="Meadows S">SM Meadows</name></author><author><name sortKey="Myers, Ct" uniqKey="Myers C">CT Myers</name></author><author><name sortKey="Krieg, Pa" uniqKey="Krieg P">PA Krieg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Val, S" uniqKey="De Val S">S De Val</name></author><author><name sortKey="Chi, Nc" uniqKey="Chi N">NC Chi</name></author><author><name sortKey="Meadows, Sm" uniqKey="Meadows S">SM Meadows</name></author><author><name sortKey="Minovitsky, S" uniqKey="Minovitsky S">S Minovitsky</name></author><author><name sortKey="Anderson, Jp" uniqKey="Anderson J">JP Anderson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bedford, Dc" uniqKey="Bedford D">DC Bedford</name></author><author><name sortKey="Kasper, Lh" uniqKey="Kasper L">LH Kasper</name></author><author><name sortKey="Fukuyama, T" uniqKey="Fukuyama T">T Fukuyama</name></author><author><name sortKey="Brindle, Pk" uniqKey="Brindle P">PK Brindle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Foulds, Ce" uniqKey="Foulds C">CE Foulds</name></author><author><name sortKey="Nelson, Ml" uniqKey="Nelson M">ML Nelson</name></author><author><name sortKey="Blaszczak, Ag" uniqKey="Blaszczak A">AG Blaszczak</name></author><author><name sortKey="Graves, Bj" uniqKey="Graves B">BJ Graves</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nelson, Ml" uniqKey="Nelson M">ML Nelson</name></author><author><name sortKey="Kang, Hs" uniqKey="Kang H">HS Kang</name></author><author><name sortKey="Lee, Gm" uniqKey="Lee G">GM Lee</name></author><author><name sortKey="Blaszczak, Ag" uniqKey="Blaszczak A">AG Blaszczak</name></author><author><name sortKey="Lau, Dk" uniqKey="Lau D">DK Lau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wei, G" uniqKey="Wei G">G Wei</name></author><author><name sortKey="Srinivasan, R" uniqKey="Srinivasan R">R Srinivasan</name></author><author><name sortKey="Cantemir Stone, Cz" uniqKey="Cantemir Stone C">CZ Cantemir-Stone</name></author><author><name sortKey="Sharma, Sm" uniqKey="Sharma S">SM Sharma</name></author><author><name sortKey="Santhanam, R" uniqKey="Santhanam R">R Santhanam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lapinski, Pe" uniqKey="Lapinski P">PE Lapinski</name></author><author><name sortKey="Kwon, S" uniqKey="Kwon S">S Kwon</name></author><author><name sortKey="Lubeck, Ba" uniqKey="Lubeck B">BA Lubeck</name></author><author><name sortKey="Wilkinson, Je" uniqKey="Wilkinson J">JE Wilkinson</name></author><author><name sortKey="Srinivasan, Rs" uniqKey="Srinivasan R">RS Srinivasan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tammela, T" uniqKey="Tammela T">T Tammela</name></author><author><name sortKey="Zarkada, G" uniqKey="Zarkada G">G Zarkada</name></author><author><name sortKey="Wallgard, E" uniqKey="Wallgard E">E Wallgard</name></author><author><name sortKey="Murtomaki, A" uniqKey="Murtomaki A">A Murtomaki</name></author><author><name sortKey="Suchting, S" uniqKey="Suchting S">S Suchting</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shikama, N" uniqKey="Shikama N">N Shikama</name></author><author><name sortKey="Lutz, W" uniqKey="Lutz W">W Lutz</name></author><author><name sortKey="Kretzschmar, R" uniqKey="Kretzschmar R">R Kretzschmar</name></author><author><name sortKey="Sauter, N" uniqKey="Sauter N">N Sauter</name></author><author><name sortKey="Roth, Jf" uniqKey="Roth J">JF Roth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yamaguchi, T" uniqKey="Yamaguchi T">T Yamaguchi</name></author><author><name sortKey="Ichise, T" uniqKey="Ichise T">T Ichise</name></author><author><name sortKey="Iwata, O" uniqKey="Iwata O">O Iwata</name></author><author><name sortKey="Hori, A" uniqKey="Hori A">A Hori</name></author><author><name sortKey="Adachi, T" uniqKey="Adachi T">T Adachi</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23284731</article-id><article-id pub-id-type="pmc">3524184</article-id><article-id pub-id-type="publisher-id">PONE-D-12-24053</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0051639</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology</subject><subj-group><subject>Developmental Biology</subject><subj-group><subject>Molecular Development</subject><subj-group><subject>Signaling</subject></subj-group></subj-group></subj-group><subj-group><subject>Molecular Cell Biology</subject><subj-group><subject>Cellular Types</subject><subj-group><subject>Endothelial Cells</subject></subj-group></subj-group><subj-group><subject>Gene Expression</subject><subj-group><subject>DNA transcription</subject><subject>Histone Modification</subject></subj-group></subj-group><subj-group><subject>Signal Transduction</subject><subj-group><subject>Signaling Cascades</subject><subj-group><subject>ERK signaling cascade</subject><subject>Tyrosine Kinase Signaling Cascade</subject></subj-group></subj-group><subj-group><subject>Signaling in Cellular Processes</subject><subj-group><subject>Ras Signaling</subject><subject>Transcriptional Signaling</subject></subj-group></subj-group><subj-group><subject>Signaling in Selected Disciplines</subject><subj-group><subject>Developmental Signaling</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine</subject><subj-group><subject>Cardiovascular</subject><subj-group><subject>Vascular Biology</subject></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Ras/MAPK Signaling Modulates VEGFR-3 Expression through Ets-Mediated p300 Recruitment and Histone Acetylation on the <italic>Vegfr3</italic> Gene in Lymphatic Endothelial Cells</article-title><alt-title alt-title-type="running-head">Ets-Mediated Modulation of <italic>Vegfr3</italic> Gene Expression</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Ichise</surname><given-names>Taeko</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Yoshida</surname><given-names>Nobuaki</given-names></name><xref ref-type="aff" rid="aff1"></xref></contrib><contrib contrib-type="author"><name><surname>Ichise</surname><given-names>Hirotake</given-names></name><xref ref-type="aff" rid="aff1"></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><addr-line>Laboratory of Developmental Genetics, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Pal</surname><given-names>Soumitro</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>Children’s Hospital Boston & Harvard Medical School, United States of America</addr-line></aff><author-notes><corresp id="cor1">* E-mail: <email>h-ichise@ims.u-tokyo.ac.jp</email></corresp><fn fn-type="conflict"><p><bold>Competing Interests: </bold>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con"><p>Conceived and designed the experiments: TI HI. Performed the experiments: TI HI. Analyzed the data: TI HI. Contributed reagents/materials/analysis tools: TI NY HI. Wrote the paper: TI HI.</p></fn></author-notes><pub-date pub-type="collection"><year>2012</year></pub-date><pub-date pub-type="epub"><day>17</day><month>12</month><year>2012</year></pub-date><volume>7</volume><issue>12</issue><elocation-id>e51639</elocation-id><history><date date-type="received"><day>9</day><month>8</month><year>2012</year></date><date date-type="accepted"><day>2</day><month>11</month><year>2012</year></date></history><permissions><copyright-year>2012</copyright-year><copyright-holder>Ichise et al</copyright-holder><license><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><abstract><p>Modulation of VEGFR-3 expression is important for altering lymphatic endothelial cell (LEC) characteristics during the lymphangiogenic processes that occur under developmental, physiological, and pathological conditions. However, the mechanisms underlying the modulation of <italic>Vegfr3</italic> gene expression remain largely unknown. Using genetically engineered mice and LECs, we demonstrated previously that Ras signaling is involved not only in VEGFR-3-induced signal transduction but also in <italic>Vegfr3</italic> gene expression. Here, we investigated the roles of the transcription factor Ets and the histone acetyltransferase p300 in LECs in Ras-mediated transcriptional regulation of <italic>Vegfr3</italic>. Ras activates Ets proteins via MAPK-induced phosphorylation. Ets knockdown, similar to Ras knockdown, resulted in a decrease in both <italic>Vegfr3</italic> transcript levels and acetylated histone H3 on the <italic>Vegfr3</italic> gene. <italic>Vegfr3</italic> knockdown results in altered LEC phenotypes, such as aberrant cell proliferation and network formation, and Ets knockdown led to milder but similar phenotypic changes. We identified evolutionarily conserved, non-coding regulatory elements within the <italic>Vegfr3</italic> gene that harbor Ets-binding motifs and have enhancer activities in LECs. Chromatin immunoprecipitation (ChIP) assays revealed that acetylated histone H3 on the regulatory elements of the <italic>Vegfr3</italic> gene was decreased following Ras and Ets knockdown, and that activated Ets proteins, together with p300, were associated with these regulatory elements, consistent with a reduction in <italic>Vegfr3</italic> gene expression in p300-knockdown LECs. Our findings demonstrate a link between Ras signaling and Ets- and p300-mediated transcriptional regulation of <italic>Vegfr3</italic>, and provide a potential mechanism by which VEGFR-3 expression levels may be modulated during lymphangiogenesis.</p></abstract><funding-group><funding-statement>This work was supported by grants from the Japan Society for the Promotion of Science (to TI. and HI) and in part by the Global COE Program “Center of Education and Research for the Advanced Genome-Based Medicine - For personalized medicine and the control of worldwide infectious diseases”, MEXT, Japan (to NY and HI).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><page-count count="15"></page-count></counts></article-meta></front></pmc><affiliations><list></list><tree><noCountry><name sortKey="Ichise, Hirotake" sort="Ichise, Hirotake" uniqKey="Ichise H" first="Hirotake" last="Ichise">Hirotake Ichise</name><name sortKey="Ichise, Taeko" sort="Ichise, Taeko" uniqKey="Ichise T" first="Taeko" last="Ichise">Taeko Ichise</name><name sortKey="Yoshida, Nobuaki" sort="Yoshida, Nobuaki" uniqKey="Yoshida N" first="Nobuaki" last="Yoshida">Nobuaki Yoshida</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/Pmc/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002761 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd -nk 002761 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= LymphedemaV1
|flux= Pmc
|étape= Checkpoint
|type= RBID
|clé= PMC:3524184
|texte= Ras/MAPK Signaling Modulates VEGFR-3 Expression through Ets-Mediated p300 Recruitment and Histone Acetylation on the Vegfr3 Gene in Lymphatic Endothelial Cells
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Checkpoint/RBID.i -Sk "pubmed:23284731" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Checkpoint/biblio.hfd \
| NlmPubMed2Wicri -a LymphedemaV1
| This area was generated with Dilib version V0.6.31. |  |