Gene expression profiling identifies HOXB4 as a direct downstream target of GATA-2 in human CD34+ hematopoietic cells.

Aplastic anemia is characterized by a reduced hematopoietic stem cell number. Although GATA-2 expression was reported to be decreased in CD34-positive cells in aplastic anemia, many questions remain regarding the intrinsic characteristics of hematopoietic stem cells in this disease. In this study, w...

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Autores principales: Tohru Fujiwara, Hisayuki Yokoyama, Yoko Okitsu, Mayumi Kamata, Noriko Fukuhara, Yasushi Onishi, Shinichi Fujimaki, Shinichiro Takahashi, Kenichi Ishizawa, Emery H Bresnick, Hideo Harigae
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:89a61d1a175b4d46bb5440315f06d2d52021-11-18T07:04:26ZGene expression profiling identifies HOXB4 as a direct downstream target of GATA-2 in human CD34+ hematopoietic cells.1932-620310.1371/journal.pone.0040959https://doaj.org/article/89a61d1a175b4d46bb5440315f06d2d52012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028422/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Aplastic anemia is characterized by a reduced hematopoietic stem cell number. Although GATA-2 expression was reported to be decreased in CD34-positive cells in aplastic anemia, many questions remain regarding the intrinsic characteristics of hematopoietic stem cells in this disease. In this study, we identified HOXB4 as a downstream target of GATA-2 based on expression profiling with human cord blood-derived CD34-positive cells infected with control or GATA-2 lentiviral shRNA. To confirm the functional link between GATA-2 and HOXB4, we conducted GATA-2 gain-of-function and loss-of-function experiments, and HOXB4 promoter analysis, including luciferase assay, in vitro DNA binding analysis and quantitative ChIP analysis, using K562 and CD34-positive cells. The analyses suggested that GATA-2 directly regulates HOXB4 expression through the GATA sequence in the promoter region. Furthermore, we assessed GATA-2 and HOXB4 expression in CD34-positive cells from patients with aplastic anemia (n = 10) and idiopathic thrombocytopenic purpura (n = 13), and demonstrated that the expression levels of HOXB4 and GATA-2 were correlated in these populations (r = 0.6573, p<0.01). Our results suggested that GATA-2 directly regulates HOXB4 expression in hematopoietic stem cells, which may play an important role in the development and/or progression of aplastic anemia.Tohru FujiwaraHisayuki YokoyamaYoko OkitsuMayumi KamataNoriko FukuharaYasushi OnishiShinichi FujimakiShinichiro TakahashiKenichi IshizawaEmery H BresnickHideo HarigaePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e40959 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Tohru Fujiwara
Hisayuki Yokoyama
Yoko Okitsu
Mayumi Kamata
Noriko Fukuhara
Yasushi Onishi
Shinichi Fujimaki
Shinichiro Takahashi
Kenichi Ishizawa
Emery H Bresnick
Hideo Harigae
Gene expression profiling identifies HOXB4 as a direct downstream target of GATA-2 in human CD34+ hematopoietic cells.
description Aplastic anemia is characterized by a reduced hematopoietic stem cell number. Although GATA-2 expression was reported to be decreased in CD34-positive cells in aplastic anemia, many questions remain regarding the intrinsic characteristics of hematopoietic stem cells in this disease. In this study, we identified HOXB4 as a downstream target of GATA-2 based on expression profiling with human cord blood-derived CD34-positive cells infected with control or GATA-2 lentiviral shRNA. To confirm the functional link between GATA-2 and HOXB4, we conducted GATA-2 gain-of-function and loss-of-function experiments, and HOXB4 promoter analysis, including luciferase assay, in vitro DNA binding analysis and quantitative ChIP analysis, using K562 and CD34-positive cells. The analyses suggested that GATA-2 directly regulates HOXB4 expression through the GATA sequence in the promoter region. Furthermore, we assessed GATA-2 and HOXB4 expression in CD34-positive cells from patients with aplastic anemia (n = 10) and idiopathic thrombocytopenic purpura (n = 13), and demonstrated that the expression levels of HOXB4 and GATA-2 were correlated in these populations (r = 0.6573, p<0.01). Our results suggested that GATA-2 directly regulates HOXB4 expression in hematopoietic stem cells, which may play an important role in the development and/or progression of aplastic anemia.
format article
author Tohru Fujiwara
Hisayuki Yokoyama
Yoko Okitsu
Mayumi Kamata
Noriko Fukuhara
Yasushi Onishi
Shinichi Fujimaki
Shinichiro Takahashi
Kenichi Ishizawa
Emery H Bresnick
Hideo Harigae
author_facet Tohru Fujiwara
Hisayuki Yokoyama
Yoko Okitsu
Mayumi Kamata
Noriko Fukuhara
Yasushi Onishi
Shinichi Fujimaki
Shinichiro Takahashi
Kenichi Ishizawa
Emery H Bresnick
Hideo Harigae
author_sort Tohru Fujiwara
title Gene expression profiling identifies HOXB4 as a direct downstream target of GATA-2 in human CD34+ hematopoietic cells.
title_short Gene expression profiling identifies HOXB4 as a direct downstream target of GATA-2 in human CD34+ hematopoietic cells.
title_full Gene expression profiling identifies HOXB4 as a direct downstream target of GATA-2 in human CD34+ hematopoietic cells.
title_fullStr Gene expression profiling identifies HOXB4 as a direct downstream target of GATA-2 in human CD34+ hematopoietic cells.
title_full_unstemmed Gene expression profiling identifies HOXB4 as a direct downstream target of GATA-2 in human CD34+ hematopoietic cells.
title_sort gene expression profiling identifies hoxb4 as a direct downstream target of gata-2 in human cd34+ hematopoietic cells.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/89a61d1a175b4d46bb5440315f06d2d5
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