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Genome-wide repress...
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Teppo, SusannaUniv Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland.
(author)
Genome-wide repression of eRNA and target gene loci by the ETV6-RUNX1 fusion in acute leukemia
- Article/chapterEnglish2016
Publisher, publication year, extent ...
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2016-09-12
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Cold Spring Harbor Laboratory,2016
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electronicrdacarrier
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LIBRIS-ID:oai:DiVA.org:uu-308904
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-308904URI
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https://doi.org/10.1101/gr.193649.115DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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De två sista författarna delar sistaförfattarskapet.
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Approximately 20%-25% of childhood acute lymphoblastic leukemias carry the ETV6-RUNX1 (E/R) fusion gene, a fusion of two central hematopoietic transcription factors, ETV6 (TEL) and RUNX1 (AML1). Despite its prevalence, the exact genomic targets of E/R have remained elusive. We evaluated gene loci and enhancers targeted by E/R genome-wide in precursor B acute leukemia cells using global run-on sequencing (GRO-seq). We show that expression of the E/R fusion leads to widespread repression of RUNX1 motif-containing enhancers at its target gene loci. Moreover, multiple super-enhancers from the CD19(+)/CD20(+)-lineage were repressed, implicating a role in impediment of lineage commitment. In effect, the expression of several genes involved in B cell signaling and adhesion was down-regulated, and the repression depended on the wild-type DNA-binding Runt domain of RUNX1. We also identified a number of E/R-regulated annotated and de novo noncoding genes. The results provide a comprehensive genome-wide mapping between E/R-regulated key regulatory elements and genes in precursor B cell leukemia that disrupt normal B lymphopoiesis.
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Laukkanen, SaaraUniv Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland.
(author)
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Liuksiala, ThomasUniv Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland.;Univ Tampere, Inst Biosci & Med Technol, Tampere 33520, Finland.
(author)
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Nordlund, JessicaUppsala Univ, Dept Med Sci, Mol Med & Sci Life Lab, S-75105 Uppsala, Sweden.
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Oittinen, MikkoUniv Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland.
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Teittinen, KaisaUniv Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland.
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Gronroos, ToniUniv Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland.
(author)
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St-Onge, PascalUniv Montreal, CHU St Justine Res Ctr, Montreal, PQ H3T 1J4, Canada.
(author)
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Sinnett, DanielUniv Montreal, CHU St Justine Res Ctr, Montreal, PQ H3T 1J4, Canada.;Univ Montreal, Fac Med, Dept Pediat, Montreal, PQ H3T 1J4, Canada.
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Syvänen, Ann-ChristineUppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab(Swepub:uu)anncsyva
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Nykter, MattiUniv Tampere, Inst Biosci & Med Technol, Tampere 33520, Finland.;Tampere Univ Technol, Dept Signal Proc, Tampere 33720, Finland.
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Viiri, KeijoUniv Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland.
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Heinaniemi, MerjaUniv Eastern Finland, Inst Biomed, Sch Med, Kuopio 70211, Finland.
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Lohi, OlliUniv Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland.
(author)
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Univ Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland.Univ Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland.;Univ Tampere, Inst Biosci & Med Technol, Tampere 33520, Finland.
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In:Genome Research: Cold Spring Harbor Laboratory26:11, s. 1468-14771088-90511549-5469
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Teppo, Susanna
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Teittinen, Kaisa
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