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Sökning: WFRF:(Bengtzén Sofia) > AML displays increa...

  • Mujahed, HuthayfaCtr Hematol & Regenerat Med, Dept Med, Huddinge, Sweden. (författare)

AML displays increased CTCF occupancy associated with aberrant gene expression and transcription factor binding

  • Artikel/kapitelEngelska2020

Förlag, utgivningsår, omfång ...

  • American Society of Hematology,2020
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-419783
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-419783URI
  • https://doi.org/10.1182/blood.2019002326DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:144275237URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • CCTC-binding factor (CTCF) is a key regulator of gene expression through organization of the chromatin structure. Still, it is unclear how CTCF binding is perturbed in leukemia or in cancer in general. We studied CTCF binding by chromatin immunoprecipitation sequencing in cells from patients with acute myeloid leukemia (AML) and in normal bone marrow (NBM) in the context of gene expression, DNA methylation, and azacitidine exposure. CTCF binding was increased in AML compared with NBM. Aberrant CTCF binding was enriched for motifs for key myeloid transcription factors such as CEBPA, PU.1, and RUNX1. AML with TET2 mutations was characterized by a particularly strong gain of CTCF binding, highly enriched for gain in promoter regions, while AML in general was enriched for changes at enhancers. There was a strong anticorrelation between CTCF binding and DNA methylation. Gain of CTCF occupancy was associated with increased gene expression; however, the genomic location (promoter vs distal regions) and enrichment of motifs (for repressing vs activating cofactors) were decisive for the gene expression pattern. Knockdown of CTCF in K562 cells caused loss of CTCF binding and transcriptional repression of genes with changed CTCF binding in AML, as well as loss of RUNX1 binding at RUNX1/CTCF-binding sites. In addition, CTCF knockdown caused increased differentiation. Azacitidine exposure caused major changes in CTCF occupancy in AML patient cells, partly by restoring a CTCF-binding pattern similar to NBM. We conclude that AML displays an aberrant increase in CTCF occupancy that targets key genes for AML development and impacts gene expression.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Miliara, SophiaKarolinska Institutet (författare)
  • Neddermeyer, Anne H.Uppsala universitet,Hematologi(Swepub:uu)annne270 (författare)
  • Bengtzen, SofiaCtr Hematol & Regenerat Med, Dept Med, Huddinge, Sweden. (författare)
  • Nilsson, ChristerKarolinska Institutet (författare)
  • Deneberg, StefanKarolinska Institutet (författare)
  • Cordeddu, LinaKarolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden. (författare)
  • Ekwall, KarlKarolinska Institutet (författare)
  • Lennartsson, AndreasKarolinska Institutet (författare)
  • Lehmann, SörenKarolinska Institutet,Uppsala universitet,Hematologi(Swepub:uu)sorle534 (författare)
  • Karolinska InstitutetCtr Hematol & Regenerat Med, Dept Med, Huddinge, Sweden. (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Blood: American Society of Hematology136:3, s. 339-3520006-49711528-0020

Internetlänk

Hitta via bibliotek

  • Blood (Sök värdpublikationen i LIBRIS)

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