Target genes and biological role of transcription factors in animal

为了了解脊椎动物各种生物现象的分子基础，在转录水平上阐明基因表达的调控是必不可少的。特定细胞系的发育和分化可以认为是多基因在不同时间点表达的级联。在本研究项目中，为了了解发育和分化的分子机制，我们分析了不同转录因子在不同细胞系中如何参与细胞的增殖、分化和凋亡。取得了以下成果。1)共抑制基因Sno突变小鼠的产生，根据细胞类型的不同，Sno既可以作为癌基因，也可以作为肿瘤抑制基因。2)两个bHLH转录因子Math3和Mash1被证明是分化为神经元的决定因素。3)控制左右不对称的转录因子Pitx2仅在左侧表达。这种表达是由**e结节信号诱导的，并由转录因子NKx2.4维持。5)转录因子GATA-3的活性受直接酰化调节。6)小分子MAF基因产物既可以是激活因子，也可以是抑制因子，这取决于它们的量。

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.