bcl-2基因主要断裂点区mbr在基因表达调控中的作用

发布时间：2018-04-09 02:05

本文选题：bcl-2基因　切入点：mbr　出处：《南京医科大学》2006年硕士论文

【摘要】：14号和18号染色体的易位即t(14；18)(q32；q21)是滤泡性淋巴瘤发生的关键步骤。位于bcl-2基因3’端非翻译区(3’-UTR)的bcl-2基因主要断裂点区(mbr)是发生该易位的主要位点。bcl-2 mbr在一定的条件下可以形成稳定的“三链”DNA(triplex DNA)结构，而“三链”DNA结构在DNA复制和基因转录活性的调控中具有重要的作用。bcl-2 mbr是核基质附着区(MAR)，，其3’端的AT丰富区是核基质蛋白SATB1结合所必须。已知SATB1还是重要的转录因子，可调节多个基因的转录活性。以上的研究表明mbr可能在bcl-2基因的表达调控中发挥重要的作用。为了研究bcl-2基因的mbr序列在调节基因活性中的作用，探讨转录因子SATB1与bcl-2 mbr功能之间的关系，我们利用荧光素酶报告基因系统在不同的细胞系中研究bcl-2 mbr对其下游报告基因活性的影响以及SATB1与mbr调控功能之间的关系。结果显示mbr可以上调报告基因的表达，去除了SATB1结合位点后的mbr即丧失了其调控基因活性的功能。在细胞中过表达SATB1可以增强mbr上调报告基因活性的作用。我们的研究结果证实bcl-2 mbr具有调节基因活性的功能，并且其功能受到转录因子SATB1的影响。
[Abstract]:The translocation of chromosomes 14 and 18, namely tm1414, Q32, Q21, is a key step in the development of follicular lymphoma.The main breakpoint of the bcl-2 gene located at the 3'-terminal untranslated region of bcl-2 gene is the main site of the translocation. Bcl-2 mbr can form a stable "triplex" DNA(triplex structure under certain conditions.The "triplex" DNA structure plays an important role in the regulation of DNA replication and gene transcriptional activity. Bcl-2 mbr is a nuclear matrix attachment region, and its 3 '-terminal AT rich region is necessary for the binding of nuclear matrix protein SATB1.SATB1 is also known as an important transcription factor that regulates the transcriptional activity of multiple genes.These studies suggest that mbr may play an important role in the regulation of bcl-2 gene expression.In order to study the role of mbr sequence of bcl-2 gene in regulating gene activity, the relationship between transcription factor SATB1 and bcl-2 mbr function was studied.We used luciferase reporter gene system to study the effect of bcl-2 mbr on the activity of downstream reporter gene in different cell lines and the relationship between SATB1 and mbr regulatory function.The results showed that mbr could up-regulate the expression of reporter gene, and mbr without SATB1 binding site lost its function of regulating gene activity.Overexpression of SATB1 in cells can enhance the up-regulation of reporter gene activity by mbr.Our results confirm that bcl-2 mbr has the function of regulating gene activity, and its function is affected by transcription factor SATB1.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R346

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