Genome-wide repression of eRNA and target gene loci by the ETV6-RUNX1 fusion in acute leukemia

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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

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2016-09-12
Cold Spring Harbor Laboratory,2016
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LIBRIS-ID:oai:DiVA.org:uu-308904
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-308904URI
https://doi.org/10.1101/gr.193649.115DOI

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Language:English
Summary in:English

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De två sista författarna delar sistaförfattarskapet.
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)
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)
Nordlund, JessicaUppsala Univ, Dept Med Sci, Mol Med & Sci Life Lab, S-75105 Uppsala, Sweden. (author)
Oittinen, MikkoUniv Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland. (author)
Teittinen, KaisaUniv Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland. (author)
Gronroos, ToniUniv Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland. (author)
St-Onge, PascalUniv Montreal, CHU St Justine Res Ctr, Montreal, PQ H3T 1J4, Canada. (author)
Sinnett, DanielUniv Montreal, CHU St Justine Res Ctr, Montreal, PQ H3T 1J4, Canada.;Univ Montreal, Fac Med, Dept Pediat, Montreal, PQ H3T 1J4, Canada. (author)
Syvänen, Ann-ChristineUppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab(Swepub:uu)anncsyva (author)
Nykter, MattiUniv Tampere, Inst Biosci & Med Technol, Tampere 33520, Finland.;Tampere Univ Technol, Dept Signal Proc, Tampere 33720, Finland. (author)
Viiri, KeijoUniv Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland. (author)
Heinaniemi, MerjaUniv Eastern Finland, Inst Biomed, Sch Med, Kuopio 70211, Finland. (author)
Lohi, OlliUniv Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland. (author)
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. (creator_code:org_t)

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In:Genome Research: Cold Spring Harbor Laboratory26:11, s. 1468-14771088-90511549-5469

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By the author/editor: Teppo, Susanna; Laukkanen, Saara; Liuksiala, Thoma ...; Nordlund, Jessic ...; Oittinen, Mikko; Teittinen, Kaisa; show more...; Gronroos, Toni; St-Onge, Pascal; Sinnett, Daniel; Syvänen, Ann-Chr ...; Nykter, Matti; Viiri, Keijo; Heinaniemi, Merj ...; Lohi, Olli; show less...

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