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Article: A quantitative proteomics approach identifies ETV6 and IKZF1 as new regulators of an ERG-driven transcriptional network

TitleA quantitative proteomics approach identifies ETV6 and IKZF1 as new regulators of an ERG-driven transcriptional network
Authors
Issue Date2016
Citation
Nucleic Acids Research, 2016, v. 44, n. 22, p. 10644-10661 How to Cite?
Abstract© The Author(s) 2016. Aberrant stem cell-like gene regulatory networks are a feature of leukaemogenesis. The ETS-related gene (ERG), an important regulator of normal haematopoiesis, is also highly expressed in T-ALL and acute myeloid leukaemia (AML). However, the transcriptional regulation of ERG in leukaemic cells remains poorly understood. In order to discover transcriptional regulators of ERG, we employed a quantitative mass spectrometry-based method to identify factors binding the 321 bp ERG +85 stem cell enhancer region in MOLT-4 T-ALL and KG-1 AML cells. Using this approach, we identified a number of known binders of the +85 enhancer in leukaemic cells along with previously unknown binders, including ETV6 and IKZF1. We confirmed that ETV6 and IKZF1 were also bound at the +85 enhancer in both leukaemic cells and in healthy human CD34+ haematopoietic stem and progenitor cells. Knockdown experiments confirmed that ETV6 and IKZF1 are transcriptional regulators not just of ERG, but also of a number of genes regulated by a densely interconnected network of seven transcription factors. At last, we show that ETV6 and IKZF1 expression levels are positively correlated with expression of a number of heptad genes in AML and high expression of all nine genes confers poorer overall prognosis.
Persistent Identifierhttp://hdl.handle.net/10722/251196
ISSN
2023 Impact Factor: 16.6
2023 SCImago Journal Rankings: 7.048
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorUnnikrishnan, Ashwin-
dc.contributor.authorGuan, Yi F.-
dc.contributor.authorHuang, Yizhou-
dc.contributor.authorBeck, Dominik-
dc.contributor.authorThoms, Julie A.I.-
dc.contributor.authorPeirs, Sofie-
dc.contributor.authorKnezevic, Kathy-
dc.contributor.authorMa, Shiyong-
dc.contributor.authorDe Walle, Inge V.-
dc.contributor.authorDe Jong, Ineke D.E.-
dc.contributor.authorAli, Zara-
dc.contributor.authorZhong, Ling-
dc.contributor.authorRaftery, Mark J.-
dc.contributor.authorTaghon, Tom-
dc.contributor.authorLarsson, Jonas-
dc.contributor.authorMacKenzie, Karen L.-
dc.contributor.authorVan Vlierberghe, Pieter-
dc.contributor.authorWong, Jason W.H.-
dc.contributor.authorPimanda, John E.-
dc.date.accessioned2018-02-01T01:54:52Z-
dc.date.available2018-02-01T01:54:52Z-
dc.date.issued2016-
dc.identifier.citationNucleic Acids Research, 2016, v. 44, n. 22, p. 10644-10661-
dc.identifier.issn0305-1048-
dc.identifier.urihttp://hdl.handle.net/10722/251196-
dc.description.abstract© The Author(s) 2016. Aberrant stem cell-like gene regulatory networks are a feature of leukaemogenesis. The ETS-related gene (ERG), an important regulator of normal haematopoiesis, is also highly expressed in T-ALL and acute myeloid leukaemia (AML). However, the transcriptional regulation of ERG in leukaemic cells remains poorly understood. In order to discover transcriptional regulators of ERG, we employed a quantitative mass spectrometry-based method to identify factors binding the 321 bp ERG +85 stem cell enhancer region in MOLT-4 T-ALL and KG-1 AML cells. Using this approach, we identified a number of known binders of the +85 enhancer in leukaemic cells along with previously unknown binders, including ETV6 and IKZF1. We confirmed that ETV6 and IKZF1 were also bound at the +85 enhancer in both leukaemic cells and in healthy human CD34+ haematopoietic stem and progenitor cells. Knockdown experiments confirmed that ETV6 and IKZF1 are transcriptional regulators not just of ERG, but also of a number of genes regulated by a densely interconnected network of seven transcription factors. At last, we show that ETV6 and IKZF1 expression levels are positively correlated with expression of a number of heptad genes in AML and high expression of all nine genes confers poorer overall prognosis.-
dc.languageeng-
dc.relation.ispartofNucleic Acids Research-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleA quantitative proteomics approach identifies ETV6 and IKZF1 as new regulators of an ERG-driven transcriptional network-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1093/nar/gkw804-
dc.identifier.pmid27604872-
dc.identifier.scopuseid_2-s2.0-85009994524-
dc.identifier.volume44-
dc.identifier.issue22-
dc.identifier.spage10644-
dc.identifier.epage10661-
dc.identifier.eissn1362-4962-
dc.identifier.isiWOS:000395742900014-
dc.identifier.issnl0305-1048-

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