Induction of erythroid-specific genes by overexpression of GATA-2 in K562 cells

被引:15
作者
Harigae, Hideo
Okitsu, Yoko
Yokoyama, Hisayuki
Fujiwara, Tohru
Inomata, Mitsue
Takahashi, Shinichiro
Minegishi, Naoko
Kaku, Mitsuo
Sasaki, Takeshi
机构
[1] Tohoku Univ, Grad Sch Med, Dept Rheumatol & Hematol, Aoba Ku, Sendai, Miyagi 9808574, Japan
[2] Tohoku Univ, Grad Sch Med, Dept Infect Control, Sendai, Miyagi 9808574, Japan
[3] Tohoku Univ, Grad Sch Med, Diagnost Lab, Sendai, Miyagi 9808574, Japan
[4] Tohoku Univ, Grad Sch Med, Biomed Engn Res Org, Sendai, Miyagi 9808574, Japan
关键词
erythroid-specific genes; GATA-2; K562; cells;
D O I
10.1532/IJH97.06020
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
GATA transcription factors have been shown to play important roles in hematopoiesis. GATA-2 is expressed in stem and progenitor cells, and has been speculated to control the proliferation and maintain the immaturity of these cells. To examine whether the function of GATA-2 is changeable according to the differentiation stage, we established GATA-2 overexpressing subclones of K562, which is a leukemic cell line committed to the erythroid lineage. Via an increase in the GATA-2 expression level, the expression levels of erythroid-specific genes including alpha-, beta-, and gamma-globin were increased compared to control cells, while the expression level of GATA-1 was unchanged. Expression of the transferrin receptor was also increased in GATA-2 overexpressing K562 cells when examined by flow cytometry. In addition, the heme content of GATA-2 overexpressing K562 cells was more than 2 times higher than control cells. Chromatin immunoprecipitation analysis showed that GATA-2 protein binding to the GATA element in alpha-globin LCR was increased in GATA-2 overexpressing K562 cells. These findings suggest that GATA-2 could induce erythroid-specific genes without competition with GATA-1 when expressed in erythroid-committed cells, and thus further suggest that temporal and spatial regulation may be important for displaying specific functions of GATA-2.
引用
收藏
页码:38 / 42
页数:5
相关论文
共 25 条
[1]   Globin gene activation during haemopoiesis is driven by protein complexes nucleated by GATA-1 and GATA-2 [J].
Anguita, E ;
Hughes, J ;
Heyworth, C ;
Blobel, GA ;
Wood, WG ;
Higgs, DR .
EMBO JOURNAL, 2004, 23 (14) :2841-2852
[2]   GATA-2/estrogen receptor chimera regulates cytokine-dependent growth of hematopoietic cells through accumulation of p21WAF1 and p27Kip1 proteins [J].
Ezoe, S ;
Matsumura, I ;
Nakata, S ;
Gale, K ;
Ishihara, K ;
Minegishi, N ;
Machii, T ;
Kitamura, T ;
Yamamoto, M ;
Enver, T ;
Kanakura, Y .
BLOOD, 2002, 100 (10) :3512-3520
[3]   Decreased expression of transcription factor GATA-2 in haematopoietic stem cells in patients with aplastic anaemia [J].
Fujimaki, S ;
Harigae, H ;
Sugawara, T ;
Takasawa, N ;
Sasaki, T ;
Kaku, M .
BRITISH JOURNAL OF HAEMATOLOGY, 2001, 113 (01) :52-57
[4]   Functional overlap of GATA-1 and GATA-2 in primitive hematopoietic development [J].
Fujiwara, Y ;
Chang, AN ;
Williams, AM ;
Orkin, SH .
BLOOD, 2004, 103 (02) :583-585
[5]   Aberrant iron accumulation and oxidized status of erythroid-specific δ-aminolevulinate synthase (ALAS2)-deficient definitive erythroblasts [J].
Harigae, H ;
Nakajima, O ;
Suwabe, N ;
Yokoyama, H ;
Furuyama, K ;
Sasaki, T ;
Kaku, M ;
Yamamoto, M ;
Sassa, S .
BLOOD, 2003, 101 (03) :1188-1193
[6]   Overexpression of GATA-2 inhibits erythroid and promotes megakaryocyte differentiation [J].
Ikonomi, P ;
Rivera, CE ;
Riordan, M ;
Washington, G ;
Schechter, AN ;
Noguchi, CT .
EXPERIMENTAL HEMATOLOGY, 2000, 28 (12) :1423-1431
[7]   Levels of GATA-1/GATA-2 transcription factors modulate expression of embryonic and fetal hemoglobins [J].
Ikonomi, P ;
Noguchi, CT ;
Miller, W ;
Kassahun, H ;
Hardison, R ;
Schechter, AN .
GENE, 2000, 261 (02) :277-287
[8]   Redirecting differentiation of hematopoietic progenitors by a transcription factor, GATA-2 [J].
Kitajima, K ;
Tanaka, M ;
Zheng, J ;
Yen, H ;
Sato, A ;
Sugiyama, D ;
Umehara, H ;
Sakai, E ;
Nakano, T .
BLOOD, 2006, 107 (05) :1857-1863
[9]   GATA-2 plays two functionally distinct roles during the ontogeny of hematopoietic stem cells [J].
Ling, KW ;
Ottersbach, K ;
van Hamburg, JP ;
Oziemlak, A ;
Tsai, FY ;
Orkin, SH ;
Ploemacher, R ;
Hendricks, RW ;
Dzierzak, E .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (07) :871-882
[10]   Rapid turnover of GATA-2 via ubiquitin-proteasome protein degradation pathway [J].
Minegishi, N ;
Suzuki, N ;
Kawatani, Y ;
Shimizu, R ;
Yamamoto, M .
GENES TO CELLS, 2005, 10 (07) :693-704