| Title |
Gene Expression Profiling Identifies HOXB4 as a Direct Downstream Target of GATA-2 in Human CD34+ Hematopoietic Cells
|
|---|---|
| Published in |
PLOS ONE, September 2012
|
| DOI | 10.1371/journal.pone.0040959 |
| Pubmed ID | |
| Authors |
Tohru Fujiwara, Hisayuki Yokoyama, Yoko Okitsu, Mayumi Kamata, Noriko Fukuhara, Yasushi Onishi, Shinichi Fujimaki, Shinichiro Takahashi, Kenichi Ishizawa, Emery H. Bresnick, Hideo Harigae |
| Abstract |
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. |
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| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 3% |
| Unknown | 32 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 8 | 24% |
| Student > Ph. D. Student | 7 | 21% |
| Other | 5 | 15% |
| Student > Bachelor | 3 | 9% |
| Student > Doctoral Student | 2 | 6% |
| Other | 6 | 18% |
| Unknown | 2 | 6% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 15 | 45% |
| Medicine and Dentistry | 7 | 21% |
| Biochemistry, Genetics and Molecular Biology | 6 | 18% |
| Economics, Econometrics and Finance | 1 | 3% |
| Nursing and Health Professions | 1 | 3% |
| Other | 0 | 0% |
| Unknown | 3 | 9% |