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  • Ullmark, ToveLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Undersökning av molekylära sjukdomsmekanismer vid blodcancer,Forskargrupper vid Lunds universitet,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Transcriptional mechanisms for the Wilms’ tumor gene 1 (WT1) oncoprotein,Lund University Research Groups (author)

Distinct global binding patterns of the Wilms' tumor gene 1 (WT1) -KTS and +KTS isoforms in leukemic cells

  • Article/chapterEnglish2017

Publisher, publication year, extent ...

  • 2016-09-09
  • Ferrata Storti Foundation (Haematologica),2017

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:cdfbbc67-8db5-4e97-868a-0a9bc5dbf088
  • https://lup.lub.lu.se/record/cdfbbc67-8db5-4e97-868a-0a9bc5dbf088URI
  • https://doi.org/10.3324/haematol.2016.149815DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:135409997URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • The zinc finger transcription factor Wilms' tumor gene 1 (WT1) acts as an oncogene in acute myeloid leukemia. A naturally occurring alternative splice event between zinc fingers three and four, removing or retaining three amino acids (+/-KTS), is believed to change the DNA binding affinity of WT1, although there are conflicting data regarding the binding affinity and motifs of the different isoforms. Increased expression of WT1 -KTS at the expense of WT1 +KTS isoform associates with poor prognosis in acute myeloid leukemia. We determined the genome-wide binding pattern of WT1 -KTS and WT1 +KTS in leukemic K562 cells by chromatin immunoprecipitation and deep sequencing (ChIP-seq). Motif discovery revealed distinct binding motifs for the isoforms, some of which have been previously reported as WT1 binding sites. We discovered that the WT1 -KTS isoform predominantly binds close to transcription start sites and to enhancers, in a similar fashion to other transcription factors, whereas WT1 +KTS binding is rather enriched within gene bodies. We observed a significant overlap between WT1 -KTS and WT1 +KTS target genes, despite the binding sites being distinct. Motif discovery revealed distinct binding motifs for the isoforms, some of which have been previously reported as WT1 binding sites. Additional analyses showed that both WT1 -KTS and WT1 +KTS target genes are more likely to be transcribed than non-targets, and are involved in cell proliferation, cell death, and development. Our study provides evidence that WT1 -KTS and WT1 +KTS share target genes yet still bind distinct locations, indicating isoform-specific regulation in transcription of genes related to cell proliferation and differentiation, consistent with involvement of WT1 in acute myeloid leukemia.

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  • Järvstråt, LinneaLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-ljt (author)
  • Sanden, CarlLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-cls (author)
  • Montano, GiorgiaLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Undersökning av molekylära sjukdomsmekanismer vid blodcancer,Forskargrupper vid Lunds universitet,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Transcriptional mechanisms for the Wilms’ tumor gene 1 (WT1) oncoprotein,Lund University Research Groups(Swepub:lu)med-ggm (author)
  • Jernmark-Nilsson, HelenaLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Undersökning av molekylära sjukdomsmekanismer vid blodcancer,Forskargrupper vid Lunds universitet,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Transcriptional mechanisms for the Wilms’ tumor gene 1 (WT1) oncoprotein,Lund University Research Groups(Swepub:lu)med-hje (author)
  • Lilljebjörn, HenrikLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)tmb-hli (author)
  • Lennartsson, AndreasKarolinska Institutet,Karolinska Institute(Swepub:lu)efor-ale (author)
  • Fioretos, ThoasLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)kgen-tfi (author)
  • Drott, KristinaLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Lymfom - Klinisk forskning,Forskargrupper vid Lunds universitet,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Lymphoma - Clinical Research,Lund University Research Groups(Swepub:lu)efor-kch (author)
  • Vidovic, KarinaLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)efor-kvi (author)
  • Nilsson, BjörnLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)klin-bni (author)
  • Gullberg, UrbanLund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Undersökning av molekylära sjukdomsmekanismer vid blodcancer,Forskargrupper vid Lunds universitet,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,Transcriptional mechanisms for the Wilms’ tumor gene 1 (WT1) oncoprotein,Lund University Research Groups(Swepub:lu)efor-ugu (author)
  • Avdelningen för hematologi och transfusionsmedicinInstitutionen för laboratoriemedicin (creator_code:org_t)

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  • In:Haematologica: Ferrata Storti Foundation (Haematologica)102:2, s. 336-3451592-87210390-6078

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