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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2012
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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) |
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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 |
work_keys_str_mv |
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