Target genes and biological role of transcription factors in animal

动物转录因子的靶基因及其生物学作用

• 批准号: 09277103
• 负责人: ISHII Shunsuke
• 金额: $ 196.99万
• 依托单位: RIKEN INSTITUTE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas (A)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09277103/
• 关键词: transcriptional control; transcriptional regulator; target genes; mutant mice; transcriptional mediators; development; hematopoietic system; neuronal system; ノックアウトマウス; 分化

To understand the molecular basis of various biological phenomena in vertebrate, it is essential to clarify the the regulation of gene expression at the transcriptional level. Development and differentiation of specific cellular lineage can be thought as a cascade of expression of multile genes at various time points. In this research project, to understand the molecular mechanism of development and differentiation, we have analyzed how various transcription factors are invoved in cellular proliferation, differentiation, and apoptosis apoptosis at various cell lineages. The following results have been obtained. 1) The mutant mice of co-repressor Sno were generated, and Sno was shown to act as the oncogene and also as a tumor suppressor suppressor depending on the cell type. 2) Two bHLH transcription factors, Math3 and Mash1, were shown to shown to function as the decision factor of differentiation into neuron. 3) Transcription factor Pitx2, which control the left-right assymetry, is expressed only in the left side. This expression is induced by the **e Nodal signali, and is maintained by transcription factor NKx2.4) Transcription factor IRF-1 was demonstrated to be tumor susceptibility gene. 5) The activity of transcription factor GATA-3 was found to to be regulated by a direct acytylation. 6) The small Maf gene products were shown to act as either activator or repressor depending on their amounts.

要了解脊椎动物中各种生物学现象的分子基础，必须阐明转录水平的基因表达的调节。特定细胞谱系的开发和分化可以被认为是在不同时间点表达多基因表达的级联。在这项研究项目中，为了了解发育和分化的分子机制，我们分析了各种细胞谱系的细胞增殖，分化和凋亡凋亡中的各种转录因子。已经获得以下结果。 1）产生了共抑制剂SNO的突变小鼠，并显示SNO充当癌基因，也是肿瘤抑制剂抑制剂，具体取决于细胞类型。 2）证明两个BHLH转录因子MATH3和MASH1可作为分化为神经元的决策因素。 3）控制左右鉴定的转录因子PITX2仅在左侧表示。该表达是由** e nodal Signali诱导的，并由转录因子NKX2.4）转录因子IRF-1保留为肿瘤易感性基因。 5）发现转录因子GATA-3的活性是由直接促型的调节。 6）小型MAF基因产物被证明可作为激活剂或阻遏物，具体取决于其量。

项目成果

Katsuoka, F., Motohashi, H., Onodera, K., Suwabe, N., Engel, J.D., and Yamamoto, M.: "One enhancer mediates mafK transcriptional activation in both hematopoietic and cardiac muscle cells."EMBO J.. 19. 2980-2991 (2000)

Katsuoka, F.、Motohashi, H.、Onodera, K.、Suwabe, N.、Engel, J.D. 和 Yamamoto, M.：“一种增强子介导造血细胞和心肌细胞中的 mafK 转录激活。”EMBO J..

Motohashi,H. 他: "Positive or negative MARE-dependent transcriptional regulation is determined by the abundance of small Maf proteins."Cell. 103. 865-875 (2000)

Motohashi, H. 等人：“MARE 依赖性转录调控是由小 Maf 蛋白的丰度决定的。”Cell. 103. 865-875 (2000)

Onodera,K.et al.: "GATA-1 transcription is controlled by distinct regulatory mechanisms during primitive and definitive erythropoiesis." Proc.Natl.Acad.Sci.USA. 390. 4487-4492 (1997)

Onodera, K. 等人：“在原始红细胞生成和最终红细胞生成过程中，GATA-1 转录受到不同调节机制的控制。”

Nozawa, H., Oda, E., Nakao, K., Ishihara, M., Ueda, S., Yokochi, T., Ogasawara, K., Nakatsuru, Y., Shimizu, S., Ohira, .Y, Hioki, K., Aizawa, S., Ishikawa, T., Katsuki, M., Muto, T., Taniguchi, T., and Tanaka. N.: "Loss of transcription factor IRF-1 affec

野泽 H.、小田 E.、中尾 K.、石原 M.、上田 S.、横内 T.、小笠原 K.、中鹤 Y.、清水 S.、大平 .Y、

Yamagata, T., Mitani, K., Oda, H., Suzuki, T., Honda, H., Asai, T., Maki, K., Nakamoto, T., and Hirai, H.: "Acetylation of GATA-3 affects T-cell survival and homing to secondary lymphoid organs."EMBO J.. 19. 4676-4687 (2000)

Yamagata, T.、Mitani, K.、Oda, H.、Suzuki, T.、Honda, H.、Asai, T.、Maki, K.、Nakamoto, T. 和 Hirai, H.：“GATA 的乙酰化