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Search: id:"swepub:oai:lup.lub.lu.se:29bda5f4-e7fc-4397-b745-b1151f59c03f" > Promoter-associated...

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  • Hamidian, ArashLund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine (author)

Promoter-associated proteins of EPAS1 identified by enChIP-MS – A putative role of HDX as a negative regulator

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • Elsevier BV,2018
  • 8 s.

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  • LIBRIS-ID:oai:lup.lub.lu.se:29bda5f4-e7fc-4397-b745-b1151f59c03f
  • https://lup.lub.lu.se/record/29bda5f4-e7fc-4397-b745-b1151f59c03fURI
  • https://doi.org/10.1016/j.bbrc.2018.03.150DOI

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  • Language:English
  • Summary in:English

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

Notes

  • Presence of perivascular neuroblastoma cells with high expression of hypoxia inducible factor (HIF)-2α correlates with distant metastasis and aggressive disease. Regulation of HIFs are traditionally considered to occur post-translationally, but we have recently shown that HIF-2α is unconventionally regulated also at the transcriptional level in neuroblastoma cells. Regulatory factors binding directly to EPAS1 (encoding HIF-2α) to promote transcription are yet to be defined. Here, we employ the novel CRISPR/Cas9-based engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) – mass spectrometry (MS) methodology to, in an unbiased fashion, identify proteins that associate with the EPAS1 promoter under normoxic and hypoxic conditions. Our enChIP analysis resulted in 27 proteins binding to the EPAS1 promoter in neuroblastoma cells. In agreement with a general hypoxia-driven downregulation of gene transcription, the majority (24 out of 27) of proteins dissociate from the promoter at hypoxia. Among them were several nucleosome-associated proteins suggesting a general opening of chromatin as one explanation to induced EPAS1 transcription at hypoxia. Of particular interest from the list of released factors at hypoxia was the highly divergent homeobox (HDX) transcription factor, that we show inversely correlates with HIF-2α in neuroblastoma cells. We propose a putative model where HDX negatively regulates EPAS1 expression through a release-of-inhibition mechanism.

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  • Vaapil, MaricaLund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-miv (author)
  • von Stedingk, KristofferLund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-kvt (author)
  • Fujita, ToshitsuguHirosaki University,Osaka University (author)
  • Persson, Camilla U.Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-cps (author)
  • Eriksson, PontusLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-pte (author)
  • Veerla, SrinivasLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)klin-sve (author)
  • De Preter, KatleenGhent University Hospital (author)
  • Speleman, FrankGhent University Hospital (author)
  • Fujii, HodakaHirosaki University,Osaka University (author)
  • Påhlman, SvenLund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)molm-spa (author)
  • Mohlin, SofieLund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Department of Clinical Sciences, Malmö,Faculty of Medicine(Swepub:lu)med-sij (author)
  • Avdelningen för translationell cancerforskningInstitutionen för laboratoriemedicin (creator_code:org_t)

Related titles

  • In:Biochemical and Biophysical Research Communications: Elsevier BV499:2, s. 291-2980006-291X

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