1995 Fiscal Year Annual Research Report

複数の転写因子による協調的な赤血球分化調節機構の解明

Research Project

Project/Area Number	07457026
Research Category	Grant-in-Aid for General Scientific Research (B)
Research Institution	University of Tsukuba
Principal Investigator	山本雅之筑波大学, 基礎医学系, 教授 (50166823)
Keywords	遺伝子発現制御 / 転写因子 / 赤血球 / GATA因子部 / NGF-E2 / Maf
Research Abstract	1.GATA因子群とNF-E2の機能解析:GATA因子群やNF-E2を発現するプラスミドを赤血球系形質を持った培養細胞株に遺伝子導入し,これらの因子を誘導的に過剰発現した際の細胞の表現形質や分化能の変化を検討した.小Maf群蛋白質MafKをマウス赤白血病(MEL)細胞に過剰発現したところ,同細胞は他の誘導剤の存在の有無に関わらず赤血球に分化した.このことから,MafKは実際に血液細胞の分化に働く転写因子であることが理解された. 2.GATA因子群およびNF-E2をコードする遺伝子の発現調節:GATA因子群のうちGATA-1とGATA-2をコードする遺伝子の転写制御解析を進めた.GATA-1の精巣型プロモーターには二つのGATA配列が存在し,それらは実際に転写活性化シグナルを媒介することができる配列であった.一方,赤血球型プロモーターの機能をトランジスジェニックマウス系を用いて検討したところ,同プロモーターと上流域2.9kbはin vivoで胎児型赤血球特異的な転写活性化を指示することが可能であることが明らかになった.また,NF-E2の小サブユニットであるMafk遺伝子の構造と機能を行い,MafK遺伝子には中胚葉特異的なプロモーター/第一エキソンと神経細胞特異的なそれとが存在することを見出した。 3.GATA遺伝子の標的遺伝子単離の試み:マウスGATA-1抗体N6はPFA固定した組織切片中のGATA-1を免疫染色できることから,MEL細胞より核を単離し,PFA固定後N6抗体で免疫沈降する方法でGATA-1の標的遺伝子の単離・同定が可能である.そこで,本方法を用いてGATA-1遺伝子の調節領域にGATA-1自身が結合していることを証明した.

Research Products
(12 results)

All Other

All Publications (12 results)

[Publications] Ishihara,H.,et al.: "Structure and regulation of the GATA-3 gene." J.Biochem.117. 499-508 (1995)
[Publications] Igarashi.K.,et al.: "Structure,expression and function of small Maf protein Mafk in mouse." J.Biol.Chem.270. 7615-7624 (1995)
[Publications] Kataoka,K.,et al.: "Smal Maf protein heterodimerizes with Fos and potentially acts as competitive repressors of NF-E2 transcription factor." Mol.Cell.Biol.15. 2180-2190 (1995)
[Publications] Igarashi,K.,et al.: "Conditional expression of ubiquitous transcription factor Mafk induces erythroleukemia cell differentiation." Proc.Natl.Acad.Sci.USA. 92. 7445-7449 (1995)
[Publications] Meguro,K.,et al.: "The role of the erythroid-specific 5-aminolevulinate synthase gene expression in erythroid heme biosynthesis." Blood. 86. 940-948 (1995)
[Publications] Ito,E.,et al.: "Expression of erythroid-specific genes in acute megakaryoblastic leukemia and transient myeloproliferative disorder in Down syndrome." Brit.J.Haematol.90. 607-614 (1995)
[Publications] Itoh,K.,et al.: "Cloning and characterization of a novel erythroid-derived CNC family transcription factor heterodimerizing with the small Mafs." Mol.Cell.Biol. 15. 4184-4193 (1995)
[Publications] Sato,A.,et al.: "Aberant progenitors common to megakaryocytic and myeloid cells in a Down's infant with transient abnormal myelopoiesis." Leukemia Res.19. 811-815 (1995)
[Publications] Jippo,T.,et al.: "Abundant expression of GATA-2 in proliferating but not in differentiated mast cells in tissues of mice." Blood. (in press).
[Publications] Motohashi,et al.: "Mesodermal-versus neuronal-specific expression of Mafk is elicited by different promoters." Genes Cells. (in press).
[Publications] Komatsu,N.,et al.: "Establishment and characterization of the thrombopoietindependent magakaryocytic cell line,UT-7/TPO." Blood. (in press).
[Publications] Igarashi,K.,et al.: "Biology of Hematopoiesis and Stem Cell Gene Transfer" INTERCEPT(Andover), 427 (1995)

1995 Fiscal Year Annual Research Report

複数の転写因子による協調的な赤血球分化調節機構の解明

Principal Investigator

山本 雅之 筑波大学, 基礎医学系, 教授 (50166823)

Research Products

[Publications] Ishihara,H.,et al.: "Structure and regulation of the GATA-3 gene." J.Biochem.117. 499-508 (1995)

[Publications] Igarashi.K.,et al.: "Structure,expression and function of small Maf protein Mafk in mouse." J.Biol.Chem.270. 7615-7624 (1995)

[Publications] Kataoka,K.,et al.: "Smal Maf protein heterodimerizes with Fos and potentially acts as competitive repressors of NF-E2 transcription factor." Mol.Cell.Biol.15. 2180-2190 (1995)

[Publications] Igarashi,K.,et al.: "Conditional expression of ubiquitous transcription factor Mafk induces erythroleukemia cell differentiation." Proc.Natl.Acad.Sci.USA. 92. 7445-7449 (1995)

[Publications] Meguro,K.,et al.: "The role of the erythroid-specific 5-aminolevulinate synthase gene expression in erythroid heme biosynthesis." Blood. 86. 940-948 (1995)

[Publications] Ito,E.,et al.: "Expression of erythroid-specific genes in acute megakaryoblastic leukemia and transient myeloproliferative disorder in Down syndrome." Brit.J.Haematol.90. 607-614 (1995)

[Publications] Itoh,K.,et al.: "Cloning and characterization of a novel erythroid-derived CNC family transcription factor heterodimerizing with the small Mafs." Mol.Cell.Biol. 15. 4184-4193 (1995)

[Publications] Sato,A.,et al.: "Aberant progenitors common to megakaryocytic and myeloid cells in a Down's infant with transient abnormal myelopoiesis." Leukemia Res.19. 811-815 (1995)

[Publications] Jippo,T.,et al.: "Abundant expression of GATA-2 in proliferating but not in differentiated mast cells in tissues of mice." Blood. (in press).

[Publications] Motohashi,et al.: "Mesodermal-versus neuronal-specific expression of Mafk is elicited by different promoters." Genes Cells. (in press).

[Publications] Komatsu,N.,et al.: "Establishment and characterization of the thrombopoietindependent magakaryocytic cell line,UT-7/TPO." Blood. (in press).

[Publications] Igarashi,K.,et al.: "Biology of Hematopoiesis and Stem Cell Gene Transfer" INTERCEPT(Andover), 427 (1995)

山本雅之筑波大学, 基礎医学系, 教授 (50166823)