Regulation of Gata1 gene expression levels during erythroid cell development

• Project/Area Number: 17590237
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Takasaki University of Health and Welfare (2006); University of Tsukuba (2005)
• Principal Investigator: KINUKO Ohneda Takasaki University of Health and Welfare, Department of Pharmacy, Professor, 薬学部, 教授 (50323291)
• Co-Investigator(Kenkyū-buntansha): 大根田 修 筑波大学, 大学院・人間総合科学研究科, 教授 (30311872)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: Cell differentiation / Transcription factor / Regulation of gene expression / erythroid cells / トランスジェニックマウス / 大腸菌人工染色体

Research Abstract

Transcription factor GATA-1 is the master regulator of erythroid cell differentiation. Expression level of the Gata1 gene changes dynamically during erythroid differentiation, and this change is essential for the proper erythropoiesis. To investigate the molecular mechanism how Gata1 gene expression changes during the erythroid lineage development, we established a novel reporter transgenic mouse system utilizing bacterial artificial chromosome containing the Gata1 gene (Gata1-BAC). In the Gata1-BAC transgenic mice, reporter gene expression faithfully recapitulates temporal and spatial expression of the Gata1 gene in a copy number-dependent but integration position-independent manner. Since the core region (235 bp) of Gata1 gene hematopoietic enhancer (G1HE), which localizes at 3.9-kbp upstream of erythroid specific IE first exon, is highly conserved between human and mouse and appeared to be important in our plasmid transgenic mouse experiments, we analyzed reporter transgenic mouse lines harboring the G1HE-Core-deficient BAC reporter transgene. Results demonstrated that G1HE-Core is essential for up-regulation of the Gata1 gene throughout the erythroid differentiation. Especially, in the absence of G1HE-Core, the expression of Gata1 is abrogated in early erythroid progenitor (EEP) stage, which corresponds to BFU-E, and in erythroblasts. On the contrary, there remains G1HE-Core-independent expression of the Gata1 gene in late erythroid progenitor (LEP) stage, which contains to CFU-E and proerythroblasts. Mutational analyses further revealed that the conserved GATA-box in G1HE-Core is essential for this enhancer activity. Thus, analyses with the Gata1-BAC reporter transgenic mouse lines demonstrate for the first time that G1HE-Core directs the stage-specific expression of the Gata1 gene in vivo.

Research Products

• [Journal Article] GATA-4 incompletely substitutes for GATA-1 in promoting both primitive and definitive erythropoiesis in vivo. (2006)
  • Author(s): Hosoya-Ohmura, S., Mochizuki, N., Suzuki, M., Ohneda, O., Ohneda K., Yamamoto M.
  • Journal Title: J Biol Chem. 281 Pages: 32820-32830
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Real-time monitoring of stress erythropoiesis in vivo using Gatal and beta-globin LCR luciferase transgenic mice. (2006)
  • Author(s): Suzuki, M., Ohneda, K., Hosoya-Ohmura, S., Tsukamoto, S., Ohneda, O., Philipsen, S., Yamamoto M.
  • Journal Title: Blood 108 Pages: 726-733
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] GATA-4 incompletely substitutes for GATA-1 in promoting both primitive and definitive erythropoiesis in vivo. (2006)
  • Author(s): Hosoya-Ohmura, S., Mochizuki, N., Suzuki, M., Ohneda, 0., Ohneda K., Yamamoto M.
  • Journal Title: J Biol Chem. 281 Pages: 32820-32830
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Real-time monitoring of stress erythropoiesis in vivo using Gata1 and beta-globin LCR luciferase transgenic mice. (2006)
  • Author(s): Suzuki, M., Ohneda, K., Hosoya-Ohmura, S., Tsukamoto, S., Ohneda, 0., Philipsen, S., Yamamoto M.
  • Journal Title: Blood 108 Pages: 726-733
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Graded levels of GATA-1 expression modulate survival, proliferation, and differentiation of erythroid progenitors. (2006)
  • Author(s): Pan, X., Ohneda, 0., Ohneda, K., Lindeboom, F., Iwata, F., Shimizu, R., Nagano, M., Suwabe, N., Philipsen, S., Lim, KC., Engel, JD., Yamamoto, M.
  • Journal Title: J Biol Chem. 280 Pages: 22385-22394
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] GATA-4 incompletely substitutes for GATA-1 in promoting both primitive and definitive erythropoiesis in vivo. (2006)
  • Author(s): Hosoya-Ohmura, S., Mochizuki, N., Suzuki, M., Ohneda K., Yamamoto M.
  • Journal Title: J Biol Chem. 281 Pages: 32820-32830
• [Journal Article] Real-time monitoring of stress erythropoiesis in vivo using Gata1 and beta-globin LCR luciferase transgenic mice. (2006)
  • Author(s): Suzuki, M., Ohneda K., Hosoya-Ohmura, S., Tsukamoto, S., Ohneda, O., Philipsen, S., Yamamoto M.
  • Journal Title: Blood 108 Pages: 726-733
• [Journal Article] Graded levels of GATA-1 expression modulate survival, proliferation, and differentiation of erythroid progenitors. (2005)
  • Author(s): Pan, X., Ohneda, O., Ohneda, K., Lindeboom, F., Iwata, F., Shimizu, R., Nagano, M., Suwabe, N., Philipsen, S., Lim, KC., Engel, JD., Yamamoto, M.
  • Journal Title: J Biol Chem. 280 Pages: 22385-22394
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Graded levels of GATA-1 expression modulate survival, proliferation, and differentiation of erythroid progenitors. (2005)
  • Author(s): Pan X, Ohneda O, Ohneda K, Lindeboom F, Iwata F, Shimizu R, Nagano M, Suwabe N, Philipsen S, Lim KC, Engel JD, Yamamoto M.
  • Journal Title: J Biol Chem 280 Pages: 22385-22394
• [Journal Article] GATA1 function, a paradigm for transcription factors in hematopoiesis. (2005)
  • Author(s): Ferreira R, Ohneda K, Yamamoto M, Philipsen S.
  • Journal Title: Mol Cell Biol. 25 Pages: 1215-1227
• [Journal Article] Transgenic over-expression of GATA-1 mutant lacking N-finger domain causes hemolytic syndrome in mouse erythroid cells. (2005)
  • Author(s): Nakano M, Ohneda K, Yamamoto-Mukai H, Shimizu R, Ohneda O, Ohmura S, Suzuki M, Tsukamoto S, Yanagawa T, Yoshida H, Takakuwa Y, Yamamoto M.
  • Journal Title: Genes Cells. 10 Pages: 47-62
• [Journal Article] Essential role of synoviolin in embryogenesis. (2005)
  • Author(s): Yagishita N, Ohneda K, Amano T, Yamasaki S, Sugiura A, Tsuchimochi K, Shin H, Kawahara K, Ohneda O, Ohta T, Tanaka S, Yamamoto M, Maruyama I, Nishioka K, Fukamizau A, Nakajima T.
  • Journal Title: J Biol Chem. 280 Pages: 7909-7916
• [Journal Article] モデル動物が切り開く造血発生研究の新展開 (2005)
  • Author(s): 大根田絹子, 山本雅之
  • Journal Title: 蛋白質・核酸・酵素 50 Pages: 633-637
• [Journal Article] Identification of functional endothelial progenitor cells suitable for the treatment of ischemic tissue using human umbilical cord blood.
  • Author(s): Nagano, M., Yamashita, T., Hamada, H., Ohneda, K., Kimura, KI., Nakagawa, T., Shibuya, M., Yoshikawa, H., Ohneda, O.
  • Journal Title: Blood (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Gata-1 self-association controls erythroid development in vivo.
  • Author(s): Shimizu, R., Trainor, CD., Nishikawa.K., Kobayashi, M., Ohneda, K., Yamamoto M.
  • Journal Title: J Biol Chem. (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Dynamic regulation of gata factor levels is more important than their identity.
  • Author(s): Ferreira, R., Wai, A., Shimizu, R., Gillemans, N., Rottier, R., Lindern, MV., Ohneda, K., Grosveld, F., Yamamoto, M., Philipsen S.
  • Journal Title: Blood (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification of functional endothelial progenitor cells suitable for the treatment of ischemic tissue using human umbilical cord blood.
  • Author(s): Nagano, M., Yamashita, T., Hamada, H., Ohneda, K., Kimura, KI., Nakagawa, T., Shibuya, M., Yoshikawa, H., Ohneda, 0.
  • Journal Title: Blood (In press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Gata-1 self-association controls erythroid development in vivo.
  • Author(s): Shimizu, R., Trainor, CD., Nishikawa, K., Kobayashi, M., Ohneda, K., Yamamoto M.
  • Journal Title: J Biol Chem. (In press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Dynamic regulation of gata factor levels is more important than their identity.
  • Author(s): Ferreira, R., Wai, A., Shimizu, R., Gillemans, N., Rottier, R., Lindern, MV., Ohneda, K., Grosveld, F., Yamamoto, M., Philipsen S.
  • Journal Title: Blood (In press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of functional endothelial progenitor cells suitable for the treatment of ischemic tissue using human umbilical cord blood.
  • Author(s): Nagano, M., Yamashita, T., Hamada, H., Ohneda, K., Kimura, KI., Nakagawa, T., Shibuya, M., Yoshikawa, H., Ohneda, O.
  • Journal Title: Blood (印刷中)
• [Journal Article] Gata-1 self-association controls erythroid development in vivo.
  • Author(s): Shimizu, R., Trainor, CD., Nishikawa, K., Kobayashi, M., Ohneda, K., Yamamoto M.
  • Journal Title: J Biol Chem. (印刷中)
• [Journal Article] Dynamic regulation of gata factor levels is more important than their identity.
  • Author(s): Ferreira, R., Wai, A., Shimizu, R., Gillemans, N., Rottier, R., Lindem, MV., Ohneda, K., Grosveld, F., Yamamoto, M., Philipsen S.
  • Journal Title: Blood (印刷中)