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A quantitative prot...
A quantitative proteomics approach identifies ETV6 and IKZF1 as new regulators of an ERG-driven transcriptional network
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- Unnikrishnan, Ashwin (author)
- University of New South Wales
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Guan, Yi F (author)
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Huang, Yizhou (author)
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- Beck, Dominik (author)
- University of Technology Sydney
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Thoms, Julie A I (author)
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- Peirs, Sofie (author)
- Ghent University
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Knezevic, Kathy (author)
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Ma, Shiyong (author)
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de Walle, Inge V (author)
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- de Jong, Ineke (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Stem Cell Center,Division of stem cell research
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- Ali, Zara (author)
- Children's Cancer Institute Australia for Medical Research
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- Zhong, Ling (author)
- University of New South Wales
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Raftery, Mark J (author)
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Taghon, Tom (author)
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- Larsson, Jonas (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Stem Cell Center,Division of stem cell research
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MacKenzie, Karen L (author)
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Van Vlierberghe, Pieter (author)
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Wong, Jason W H (author)
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- Pimanda, John E (author)
- Prince of Wales Hospital
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(creator_code:org_t)
- 2016-09-06
- 2016
- English.
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 44:22, s. 10644-10661
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Keyword
- Base Sequence
- Binding Sites
- Cell Line, Tumor
- Consensus Sequence
- Enhancer Elements, Genetic
- Gene Expression Regulation, Leukemic
- Gene Regulatory Networks
- Humans
- Ikaros Transcription Factor/physiology
- Kaplan-Meier Estimate
- Leukemia, Myeloid, Acute/genetics
- Prognosis
- Proportional Hazards Models
- Protein Binding
- Proteome
- Proteomics
- Proto-Oncogene Proteins c-ets/physiology
- Repressor Proteins/physiology
- Transcription, Genetic
- Transcriptional Regulator ERG/physiology
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Unnikrishnan, As ...
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Guan, Yi F
-
Huang, Yizhou
-
Beck, Dominik
-
Thoms, Julie A I
-
Peirs, Sofie
-
show more...
-
Knezevic, Kathy
-
Ma, Shiyong
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de Walle, Inge V
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de Jong, Ineke
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Ali, Zara
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Zhong, Ling
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Raftery, Mark J
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Taghon, Tom
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Larsson, Jonas
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MacKenzie, Karen ...
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Van Vlierberghe, ...
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Wong, Jason W H
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Pimanda, John E
-
show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Microbiology in ...
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Nucleic Acids Re ...
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Lund University