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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Dual requirement for the ETS transcription factors Fli-1 and Erg in hematopoietic stem cells and the megakaryocyte lineage</title><author><name sortKey="Kruse, Elizabeth A" sort="Kruse, Elizabeth A" uniqKey="Kruse E" first="Elizabeth A." last="Kruse">Elizabeth A. Kruse</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia;</nlm:aff></affiliation></author><author><name sortKey="Loughran, Stephen J" sort="Loughran, Stephen J" uniqKey="Loughran S" first="Stephen J." last="Loughran">Stephen J. Loughran</name><affiliation><nlm:aff id="aff3">Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Cancer and Haematology, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3052, Australia;</nlm:aff></affiliation></author><author><name sortKey="Baldwin, Tracey M" sort="Baldwin, Tracey M" uniqKey="Baldwin T" first="Tracey M." last="Baldwin">Tracey M. Baldwin</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Josefsson, Emma C" sort="Josefsson, Emma C" uniqKey="Josefsson E" first="Emma C." last="Josefsson">Emma C. Josefsson</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Ellis, Sarah" sort="Ellis, Sarah" uniqKey="Ellis S" first="Sarah" last="Ellis">Sarah Ellis</name><affiliation><nlm:aff id="aff4">Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne 3002, Australia;</nlm:aff></affiliation></author><author><name sortKey="Watson, Dennis K" sort="Watson, Dennis K" uniqKey="Watson D" first="Dennis K." last="Watson">Dennis K. Watson</name><affiliation><nlm:aff wicri:cut="; and" id="aff5">Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425</nlm:aff></affiliation></author><author><name sortKey="Nurden, Paquita" sort="Nurden, Paquita" uniqKey="Nurden P" first="Paquita" last="Nurden">Paquita Nurden</name><affiliation><nlm:aff id="aff6">Centre de Référence des Pathologies Plaquettaires, Plateforme Technologique et d'Innovation Biomédicale, Hôpital Xavier Arnozan, 33600 Pessac, France</nlm:aff></affiliation></author><author><name sortKey="Metcalf, Donald" sort="Metcalf, Donald" uniqKey="Metcalf D" first="Donald" last="Metcalf">Donald Metcalf</name><affiliation><nlm:aff id="aff2">Cancer and Haematology, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3052, Australia;</nlm:aff></affiliation></author><author><name sortKey="Hilton, Douglas J" sort="Hilton, Douglas J" uniqKey="Hilton D" first="Douglas J." last="Hilton">Douglas J. Hilton</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia;</nlm:aff></affiliation></author><author><name sortKey="Alexander, Warren S" sort="Alexander, Warren S" uniqKey="Alexander W" first="Warren S." last="Alexander">Warren S. Alexander</name><affiliation><nlm:aff id="aff2">Cancer and Haematology, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3052, Australia;</nlm:aff></affiliation></author><author><name sortKey="Kile, Benjamin T" sort="Kile, Benjamin T" uniqKey="Kile B" first="Benjamin T." last="Kile">Benjamin T. Kile</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19666492</idno><idno type="pmc">2728977</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728977</idno><idno type="RBID">PMC:2728977</idno><idno type="doi">10.1073/pnas.0906556106</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">001B29</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001B29</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Dual requirement for the ETS transcription factors Fli-1 and Erg in hematopoietic stem cells and the megakaryocyte lineage</title><author><name sortKey="Kruse, Elizabeth A" sort="Kruse, Elizabeth A" uniqKey="Kruse E" first="Elizabeth A." last="Kruse">Elizabeth A. Kruse</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia;</nlm:aff></affiliation></author><author><name sortKey="Loughran, Stephen J" sort="Loughran, Stephen J" uniqKey="Loughran S" first="Stephen J." last="Loughran">Stephen J. Loughran</name><affiliation><nlm:aff id="aff3">Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia;</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Cancer and Haematology, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3052, Australia;</nlm:aff></affiliation></author><author><name sortKey="Baldwin, Tracey M" sort="Baldwin, Tracey M" uniqKey="Baldwin T" first="Tracey M." last="Baldwin">Tracey M. Baldwin</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Josefsson, Emma C" sort="Josefsson, Emma C" uniqKey="Josefsson E" first="Emma C." last="Josefsson">Emma C. Josefsson</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Ellis, Sarah" sort="Ellis, Sarah" uniqKey="Ellis S" first="Sarah" last="Ellis">Sarah Ellis</name><affiliation><nlm:aff id="aff4">Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne 3002, Australia;</nlm:aff></affiliation></author><author><name sortKey="Watson, Dennis K" sort="Watson, Dennis K" uniqKey="Watson D" first="Dennis K." last="Watson">Dennis K. Watson</name><affiliation><nlm:aff wicri:cut="; and" id="aff5">Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425</nlm:aff></affiliation></author><author><name sortKey="Nurden, Paquita" sort="Nurden, Paquita" uniqKey="Nurden P" first="Paquita" last="Nurden">Paquita Nurden</name><affiliation><nlm:aff id="aff6">Centre de Référence des Pathologies Plaquettaires, Plateforme Technologique et d'Innovation Biomédicale, Hôpital Xavier Arnozan, 33600 Pessac, France</nlm:aff></affiliation></author><author><name sortKey="Metcalf, Donald" sort="Metcalf, Donald" uniqKey="Metcalf D" first="Donald" last="Metcalf">Donald Metcalf</name><affiliation><nlm:aff id="aff2">Cancer and Haematology, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3052, Australia;</nlm:aff></affiliation></author><author><name sortKey="Hilton, Douglas J" sort="Hilton, Douglas J" uniqKey="Hilton D" first="Douglas J." last="Hilton">Douglas J. Hilton</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia;</nlm:aff></affiliation></author><author><name sortKey="Alexander, Warren S" sort="Alexander, Warren S" uniqKey="Alexander W" first="Warren S." last="Alexander">Warren S. Alexander</name><affiliation><nlm:aff id="aff2">Cancer and Haematology, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3052, Australia;</nlm:aff></affiliation></author><author><name sortKey="Kile, Benjamin T" sort="Kile, Benjamin T" uniqKey="Kile B" first="Benjamin T." last="Kile">Benjamin T. Kile</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Fli-1 and Erg are closely related members of the Ets family of transcription factors. Both genes are translocated in human cancers, including Ewing's sarcoma, leukemia, and in the case of <italic>Erg</italic>, more than half of all prostate cancers. Although evidence from mice and humans suggests that <italic>Fli-1</italic> is required for megakaryopoiesis, and that <italic>Erg</italic> is required for normal adult hematopoietic stem cell (HSC) regulation, their precise physiological roles remain to be defined. To elucidate the relationship between <italic>Fli-1</italic> and <italic>Erg</italic> in hematopoiesis, we conducted an analysis of mice carrying mutations in both genes. Our results demonstrate that there is a profound genetic interaction between <italic>Fli-1</italic> and <italic>Erg</italic>. Double heterozygotes displayed phenotypes more dramatic than single heterozygotes: severe thrombocytopenia, with a significant deficit in megakaryocyte numbers and evidence of megakaryocyte dysmorphogenesis, and loss of HSCs accompanied by a reduction in the number of committed hematopoietic progenitor cells. These results illustrate an indispensable requirement for both Fli-1 and Erg in normal HSC and megakaryocyte homeostasis, and suggest these transcription factors may coregulate common target genes.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Proc Natl Acad Sci U S A</journal-id><journal-id journal-id-type="hwp">pnas</journal-id><journal-id journal-id-type="pmc">pnas</journal-id><journal-id journal-id-type="publisher-id">PNAS</journal-id><journal-title-group><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title></journal-title-group><issn pub-type="ppub">0027-8424</issn><issn pub-type="epub">1091-6490</issn><publisher><publisher-name>National Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">19666492</article-id><article-id pub-id-type="pmc">2728977</article-id><article-id pub-id-type="publisher-id">8961</article-id><article-id pub-id-type="doi">10.1073/pnas.0906556106</article-id><article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject><subj-group><subject>Cell Biology</subject></subj-group></subj-group></article-categories><title-group><article-title>Dual requirement for the ETS transcription factors Fli-1 and Erg in hematopoietic stem cells and the megakaryocyte lineage</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Kruse</surname><given-names>Elizabeth A.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff3"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Loughran</surname><given-names>Stephen J.</given-names></name><xref ref-type="aff" rid="aff3"><sup>b</sup></xref><xref ref-type="aff" rid="aff2"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Baldwin</surname><given-names>Tracey M.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Josefsson</surname><given-names>Emma C.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ellis</surname><given-names>Sarah</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Watson</surname><given-names>Dennis K.</given-names></name><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nurden</surname><given-names>Paquita</given-names></name><xref ref-type="aff" rid="aff6"><sup>f</sup></xref></contrib><contrib contrib-type="author"><name><surname>Metcalf</surname><given-names>Donald</given-names></name><xref ref-type="aff" rid="aff2"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hilton</surname><given-names>Douglas J.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff3"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Alexander</surname><given-names>Warren S.</given-names></name><xref ref-type="aff" rid="aff2"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kile</surname><given-names>Benjamin T.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><aff id="aff1">Divisions of<sup>a</sup>Molecular Medicine and</aff><aff id="aff2"><sup>c</sup>Cancer and Haematology, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3052, Australia;</aff><aff id="aff3"><sup>b</sup>Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia;</aff><aff id="aff4"><sup>d</sup>Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne 3002, Australia;</aff><aff id="aff5"><sup>e</sup>Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425; and</aff><aff id="aff6"><sup>f</sup>Centre de Référence des Pathologies Plaquettaires, Plateforme Technologique et d'Innovation Biomédicale, Hôpital Xavier Arnozan, 33600 Pessac, France</aff></contrib-group><author-notes><corresp id="cor1"><sup>1</sup>To whom correspondence may be addressed. E-mail: <email>kile@wehi.edu.au</email> or <email>metcalf@wehi.edu.au</email></corresp><fn fn-type="con"><p>Contributed by Donald Metcalf, June 16, 2009</p></fn><fn fn-type="con"><p>Author contributions: E.A.K., S.J.L., E.C.J., D.J.H., W.S.A., and B.T.K. designed research; E.A.K., T.M.B., S.E., W.S.A., and B.T.K. performed research; D.K.W. contributed new reagents/analytic tools; E.A.K., S.J.L., E.C.J., S.E., P.N., D.M., D.J.H., W.S.A., and B.T.K. analyzed data; and E.A.K., W.S.A., and B.T.K. wrote the paper.</p></fn></author-notes><pub-date pub-type="ppub"><day>18</day><month>8</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>31</day><month>7</month><year>2009</year></pub-date><volume>106</volume><issue>33</issue><fpage>13814</fpage><lpage>13819</lpage><history><date date-type="received"><day>4</day><month>5</month><year>2009</year></date></history><permissions></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zpq03309013814.pdf"></self-uri><abstract><p>Fli-1 and Erg are closely related members of the Ets family of transcription factors. Both genes are translocated in human cancers, including Ewing's sarcoma, leukemia, and in the case of <italic>Erg</italic>, more than half of all prostate cancers. Although evidence from mice and humans suggests that <italic>Fli-1</italic> is required for megakaryopoiesis, and that <italic>Erg</italic> is required for normal adult hematopoietic stem cell (HSC) regulation, their precise physiological roles remain to be defined. To elucidate the relationship between <italic>Fli-1</italic> and <italic>Erg</italic> in hematopoiesis, we conducted an analysis of mice carrying mutations in both genes. Our results demonstrate that there is a profound genetic interaction between <italic>Fli-1</italic> and <italic>Erg</italic>. Double heterozygotes displayed phenotypes more dramatic than single heterozygotes: severe thrombocytopenia, with a significant deficit in megakaryocyte numbers and evidence of megakaryocyte dysmorphogenesis, and loss of HSCs accompanied by a reduction in the number of committed hematopoietic progenitor cells. These results illustrate an indispensable requirement for both Fli-1 and Erg in normal HSC and megakaryocyte homeostasis, and suggest these transcription factors may coregulate common target genes.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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