1996 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 Institution	University of Tsukuba
Principal Investigator	山本雅之筑波大学, 基礎医学系, 教授 (50166823)
Keywords	転写因子 / 赤血球 / 細胞分化 / GATA-1 / GATA-2 / NF-E2 / CNCファミリー / 造血幹細胞
Research Abstract	転写因子群による細胞特異的な遺伝子発現制御機構を解明する目的で,赤血球系をモデルとして取り上げ,転写因子間相互作用に基づく転写制御ネットワークが赤血球系前駆細胞の増殖・分化の方向性決定に果たす役割の解明と,赤血球系転写因子自身の発現制御機構の解明とを試み、以下の点を明らかにした. 1.GATA-1の転写制御機構が胎児型造血細胞と成人型造血細胞とで異なることを発現した. 2.GATA-1遺伝子の部分破壊により,同遺伝子が胎児型造血細胞・成人型造血細胞のそれぞれの成熟過程に必須であることを発見した. 3.NF-E2転写因子の小サブユニットであるMafKの転写が,造血細胞,間葉細胞と神経細胞とで異なるプロモーターにより,独立に制御されることを発見した. 4.NF-E2の大サブユニットであるCNCファミリー蛋白質と会合し,その細胞内局在を制御する新しい蛋白質Keaplを発見した. 5.GATA-2遺伝子の転写制御には2つの異なるプロモーターが関与しており,造血細胞で特異的に機能するプロモーターが存在することを明らかにした. 本研究において,胎児造血細胞と成人造血細胞との間でGATA-1遺伝子の転写制御機構が異なっていることが明らかになった.このことは,両造血細胞系列の発生過程における違いを強く示唆するものである.今後は、これらの制御に関与する遺伝子調節領域の同定と,そこに作用する転写因子群の解析を行う予定である.

Research Products
(16 results)

All Other

All Publications (16 results)

[Publications] Jippo,T.: "Abundant expression of GATA-2 in proliferating but not in differentaited mast cells in tissues of mice;demonstration by in situ bybridzation." Biood. 87巻. 993-998 (1996)
[Publications] Motohashi,H.: "Mesodermal-vosus neuranal-specific expression of Mafk is elicited by different promoters." Genes Cells. 1巻. 223-238 (1996)
[Publications] Komatsu,N.: "Establishment and characterization of the thrombopoietin-dependent magakaryocytic cell line,VT7/TPO." Blood. 87巻. 4552-4560 (1996)
[Publications] Toki,T.: "Abundant expression of erythroid transcription factor p45 NF-E2 mRNA in human peripheral granulocytes." Biochem.Biophys.Res.Commun.219巻. 760-765 (1996)
[Publications] Oyake,T.: "A novel family of BTB-bZip transcription factors BACH that interact with MafK and regulate transcribtion through NF-E2 site." Mol.Cell.Biol.16巻. 6083-6095 (1996)
[Publications] Kato,S.: "Differentiation-dependent enhanced expression of protein phosphatase 2Cin germ cells of mouse seminiferous tubules." FEBS Lett.396巻. 293-297 (1996)
[Publications] Ohtsu,H: "Histidine decarboxylase expression in mouse mast cell line P815 is induced by mouse peritoreal cavity incubation" J.Biol.Chem.271巻. 28439-28444 (1996)
[Publications] Minegishi,N: "Expression of GATA transcription factors in myelogenous and lymphoblastic leakemia cells." Int.J.Hematol. (印刷中).
[Publications] Nagai,M: "Novel regulation of d-aminolevulinate synthanse rat Harderian giand." Biochem.Pharmacol.(印刷中).
[Publications] Onodera,K: "Conserved stracture,regulatory elements and transcriptional regulation from the GATA-1 gene testis promoter" J.Biochem.121巻. 251-263 (1997)
[Publications] Toki,T: "Human small Maf proteins from neterodimers with CNC family transcription factors and recognize NF-E2 motif" Oncogene. (印刷中).
[Publications] Nagai,T.: "5-Aminolevulinate synthase expression and hemoglotin synthesis in a human myelogerous leakemia cell line" J.Biochem. 121巻. 487-495 (1997)
[Publications] Imagawa,S: "Negative regulation of the erythropoietin gene expression by the GATA transcription factors." Blood. (印刷中).
[Publications] Yamamoto,M: "Upstream and dornstream of erythrOid transcription factor GATA-1." Genes to Cells. (印刷中).
[Publications] Takahashi,S: "Arrest in erythroid cell development by promoter-specific disruption of GATA-1 gene" J.Biol.Chem.(印刷中).
[Publications] Onodera,K: "Gata-1 transcription in controiled by distinct regulatory mechanisms during primitive and definitie erythropoiesis." Proc.Natl.Acad.Sci.USA. (印刷中).

1996 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] Jippo,T.: "Abundant expression of GATA-2 in proliferating but not in differentaited mast cells in tissues of mice;demonstration by in situ bybridzation." Biood. 87巻. 993-998 (1996)

[Publications] Motohashi,H.: "Mesodermal-vosus neuranal-specific expression of Mafk is elicited by different promoters." Genes Cells. 1巻. 223-238 (1996)

[Publications] Komatsu,N.: "Establishment and characterization of the thrombopoietin-dependent magakaryocytic cell line,VT7/TPO." Blood. 87巻. 4552-4560 (1996)

[Publications] Toki,T.: "Abundant expression of erythroid transcription factor p45 NF-E2 mRNA in human peripheral granulocytes." Biochem.Biophys.Res.Commun.219巻. 760-765 (1996)

[Publications] Oyake,T.: "A novel family of BTB-bZip transcription factors BACH that interact with MafK and regulate transcribtion through NF-E2 site." Mol.Cell.Biol.16巻. 6083-6095 (1996)

[Publications] Kato,S.: "Differentiation-dependent enhanced expression of protein phosphatase 2Cin germ cells of mouse seminiferous tubules." FEBS Lett.396巻. 293-297 (1996)

[Publications] Ohtsu,H: "Histidine decarboxylase expression in mouse mast cell line P815 is induced by mouse peritoreal cavity incubation" J.Biol.Chem.271巻. 28439-28444 (1996)

[Publications] Minegishi,N: "Expression of GATA transcription factors in myelogenous and lymphoblastic leakemia cells." Int.J.Hematol. (印刷中).

[Publications] Nagai,M: "Novel regulation of d-aminolevulinate synthanse rat Harderian giand." Biochem.Pharmacol.(印刷中).

[Publications] Onodera,K: "Conserved stracture,regulatory elements and transcriptional regulation from the GATA-1 gene testis promoter" J.Biochem.121巻. 251-263 (1997)

[Publications] Toki,T: "Human small Maf proteins from neterodimers with CNC family transcription factors and recognize NF-E2 motif" Oncogene. (印刷中).

[Publications] Nagai,T.: "5-Aminolevulinate synthase expression and hemoglotin synthesis in a human myelogerous leakemia cell line" J.Biochem. 121巻. 487-495 (1997)

[Publications] Imagawa,S: "Negative regulation of the erythropoietin gene expression by the GATA transcription factors." Blood. (印刷中).

[Publications] Yamamoto,M: "Upstream and dornstream of erythrOid transcription factor GATA-1." Genes to Cells. (印刷中).

[Publications] Takahashi,S: "Arrest in erythroid cell development by promoter-specific disruption of GATA-1 gene" J.Biol.Chem.(印刷中).

[Publications] Onodera,K: "Gata-1 transcription in controiled by distinct regulatory mechanisms during primitive and definitie erythropoiesis." Proc.Natl.Acad.Sci.USA. (印刷中).

山本雅之筑波大学, 基礎医学系, 教授 (50166823)