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.

为了了解脊椎动物各种生物现象的分子基础，有必要从转录水平上阐明基因表达的调控。特定细胞谱系的发育和分化可以被认为是多个基因在不同时间点的级联表达。在本研究项目中，为了了解发育和分化的分子机制，我们分析了各种转录因子在不同细胞系中如何参与细胞增殖、分化和凋亡。得到了以下结果：1)产生了共抑制因子Sno的突变小鼠，并且根据不同的细胞类型，Sno既可以作为致癌基因，也可以作为肿瘤抑制因子。2)两个bHLH转录因子Math3和Mash1被证明是神经元分化的决定因子。3)控制左右不对称的转录因子Pitx2仅在左侧表达。该表达由**e节点信号诱导，并由转录因子NKx2.4维持。)转录因子IRF-1被证实为肿瘤易感基因。5)发现转录因子GATA-3的活性受直接乙酰化调控。6)小Maf基因产物的激活或抑制作用取决于它们的数量。

项目成果

Nomura, T., Khan, M.M., Kaul, S.C., Dong, H.D., Wadhwa, R., Colmenares, C., Kohn, I., and Ishii, S.: "Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor."Genes Dev.. 13. 412-42

Nomura, T.、Khan, M.M.、Kaul, S.C.、Dong, H.D.、Wadhwa, R.、Colmenares, C.、Kohn, I. 和 Ishii, S.：“Ski 是组蛋白脱乙酰酶复合物的组成部分，

Saijoh, Y., Adachi, H., Sakuma, R., Yeo, C.Y., Yashiro, K., Watanabe, M., Hashiguchi, H., Mochida, K., Ohishi, S., Kawabata, M., Miyazono, K., Whitman, M., and Hamada, H.: "Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pat

Saijoh, Y.、Adachi, H.、Sakuma, R.、Yeo, C.Y.、Yashiro, K.、Watanabe, M.、Hashiguchi, H.、Mochida, K.、Ohishi, S.、Kawabata, M.、Miyazono

Nomura, T. et al.: "Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor"Genes Dev.. 13. 412-423 (1999)

Nomura, T. 等人：“Ski 是 Mad 和甲状腺激素受体转录抑制所需的组蛋白脱乙酰酶复合物的一个组成部分”Genes Dev.. 13. 412-423 (1999)

Nozawa, H. et al.: "Loss of transcription factor IRF-l affects tumor susceptibility in mice carrying the Ha-ras transgene or nullizygosity for p53"Genes Dev.. 13. 1240-1245 (1999)

Nozawa, H.等人：“转录因子IRF-1的丢失影响携带Ha-ras转基因或p53失效的小鼠的肿瘤易感性”Genes Dev.. 13. 1240-1245 (1999)

Nakagoshi,H.et al.: "Defective proventriculus encodes a novel homeodomain protein required for the functional specification in Drosophila midgut" Gene Dev.12. 2724-2734 (1998)

Nakagoshi,H.et al.：“有缺陷的腺胃编码果蝇中肠功能规范所需的新型同源域蛋白”Gene Dev.12。