The structure of aldolase isozyme genes and the regulation of their tissue-specific expression

醛缩酶同工酶基因的结构及其组织特异性表达的调控

• 批准号: 60470142
• 负责人: KIICHI Ishikawa
• 金额: $ 3.2万
• 依托单位: Yamagata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-60470142/
• 关键词: Aldolase B gene; Regulation of gene expression; DNase I hyper sensitive region; DNAメチレーション

By examining the tissues and cells which express or do not express aldolase B gene, the relationship between the gene expression and chromatin structure and DNA methylation of aldolase B gene was studied. Following results were obtained. (1) The examination of the chromatin structure of aldolase B locus by DNase I hypersensitivity revealed that the specific structure which is sensitive to DNase I at about 0.3 Kb upstream from the transcription-initiation site is necessary for transcription of the gene. (2) Out of 15 Hpa <II> and Hha <I> sites in and around the gene, those sites which located at 3'-half and at downstream of the gene were heavily methylated, regardless of the gene expression. A Hha <I> site in the 5'-flanking region, and several Hpa <II> sites in the first intron were hypomethylated in liver and differentiated hepatoma, while they were heavily methylated in brain and undifferentiated hepatoma. These facts suggest that the hypomethylation of cytosine residue at specific sites in the 5'-flanking and the 5'-half regions of the gene are related to the expression of this gene. Our recent results suggest that, besides loosened chromatin structure and hypomethylation, some trans-acting factor(s) which interact with the element in this region are necessary for the transcription of this gene.

通过检测表达和不表达醛缩酶B基因的组织和细胞，研究基因表达与醛缩酶B基因的染色质结构和DNA甲基化的关系。获得了以下结果。(1)通过DNA酶I超敏反应对醛缩酶B位点的染色质结构的检查表明，在转录起始位点上游约0.3 K B处对DNA酶I敏感的特异性结构是该基因转录所必需的。(2)在<II><I>该基因内部和周围的15个Hpa和Hha位点中，位于该基因3 '半和下游的那些位点高度甲基化，而与基因表达无关。在<I>肝和分化型肝癌中，5 '侧翼区的一个Hha位点和<II>第一内含子中的几个Hpa位点甲基化程度较低，而在脑和未分化型肝癌中，它们甲基化程度较高。这些事实表明，在该基因的5 '-侧翼和5'-半区域的特定位点的胞嘧啶残基的低甲基化与该基因的表达有关。我们最近的研究结果表明，除了松散的染色质结构和低甲基化，一些反式作用因子与该区域的元件相互作用是必要的该基因的转录。

项目成果

K.Tsutsumi; T.Mukai; S.Hidaka; H.Miyahara; R.Tsutsumi; T.Tanaka; K.Hori; K.Ishikawa: "Structure and genomic organization of the rat aldolase B gene" Journal of Molecular Biology. 181. 153-160 (1985)

K.堤;

石川喜一: 蛋白質 核酸 酵素. 31. 201-205 (1986)

石川喜一：蛋白质、核酸、酶。31. 201-205 (1986)

Isozymes: Current topics in biological and medical research (C.L.Markert ed.) K.Tsutsumi, R.Tsutsumi, M.Daimon, M.Numazaki, K.Ishikawa: Alan R. Liss Inc., New York. Tissue-specific and developmentally specific controls involved in rat aldolase B gene expr

同工酶：生物和医学研究的当前主题（C.L.Markert 编辑）K.Tsutsumi、R.Tsutsumi、M.Daimon、M.Numazaki、K.Ishikawa：Alan R. Liss Inc.，纽约。

J.Sato; K.Tsutsumi; M.Ishikawa; K.Ishikawa: "Dietary regulation of aldolase isozyme expression in rat intestinal mucosa" Archives of Biochemistry and Biophysics. 253. (1987)

J·佐藤；

K.Tsutsumi; R.Tsutsumi; K.Ishikawa: "Tissue-specific chromatin structure of the rat aldolase B locus" Journal of Biochemistry.

K.堤;