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Genome-wide repress...
Genome-wide repression of eRNA and target gene loci by the ETV6-RUNX1 fusion in acute leukemia
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- Teppo, Susanna (författare)
- Univ Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland.
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- Laukkanen, Saara (författare)
- Univ Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland.
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- Liuksiala, Thomas (författare)
- 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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- Nordlund, Jessica (författare)
- Uppsala Univ, Dept Med Sci, Mol Med & Sci Life Lab, S-75105 Uppsala, Sweden.
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- Oittinen, Mikko (författare)
- Univ Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland.
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- Teittinen, Kaisa (författare)
- Univ Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland.
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- Gronroos, Toni (författare)
- Univ Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland.
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- St-Onge, Pascal (författare)
- Univ Montreal, CHU St Justine Res Ctr, Montreal, PQ H3T 1J4, Canada.
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- Sinnett, Daniel (författare)
- Univ 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-Christine (författare)
- Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab
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- Nykter, Matti (författare)
- Univ Tampere, Inst Biosci & Med Technol, Tampere 33520, Finland.;Tampere Univ Technol, Dept Signal Proc, Tampere 33720, Finland.
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- Viiri, Keijo (författare)
- Univ Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland.
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- Heinaniemi, Merja (författare)
- Univ Eastern Finland, Inst Biomed, Sch Med, Kuopio 70211, Finland.
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- Lohi, Olli (författare)
- Univ Tampere, Tampere Ctr Child Hlth Res, Tampere 33520, Finland.;Tampere Univ Hosp, Tampere 33520, Finland.
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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. (creator_code:org_t)
- 2016-09-12
- 2016
- Engelska.
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 26:11, s. 1468-1477
- Relaterad länk:
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https://uu.diva-port... (primary) (Raw object)
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http://genome.cshlp....
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
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- art (ämneskategori)
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Teppo, Susanna
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Laukkanen, Saara
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Liuksiala, Thoma ...
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Nordlund, Jessic ...
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Oittinen, Mikko
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Teittinen, Kaisa
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visa fler...
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Gronroos, Toni
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St-Onge, Pascal
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Sinnett, Daniel
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Syvänen, Ann-Chr ...
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Nykter, Matti
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Viiri, Keijo
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Heinaniemi, Merj ...
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Lohi, Olli
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