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    Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/9464


    Title: 由分子層面探討ZFP42之轉錄抑制機制
    Authors: 姚雅莉
    Contributors: 健康學院
    生物科技學系
    Date: 2006
    Issue Date: 2010-05-07 07:39:49 (UTC+0)
    Abstract: ZFP42是一個 zinc-finger 蛋白,類似果蠅 Krüpple 家族,一般常用來標定特定胚
    胎發育過程,但是至今 ZFP42 的功能幾乎是完全未知的。我們先前發現 ZFP42 是一個轉錄抑制因子,今年我們更找出免疫球蛋白 κ 輕鍊的 enhancer 為 ZFP42 的下游基因,並且發現 ZFP42 可以與組蛋白去乙醯、組蛋白轉甲基、以及聚腺核甘二磷酸聚合結合行交互作用。研究顯示組蛋白去乙醯、特定的組蛋白轉甲基、以及組蛋白與轉錄因子的聚腺核甘二磷酸聚合修飾作用對於染色質的凝聚緊縮與接下來的轉錄抑制作用有強烈的因果關係。在這份計劃書中,我們想要從分子層面來探討 ZFP42 的轉錄抑制機制。我的假說是:ZFP42 藉由與修飾染色質的蛋白行交互作用來改變其下游基因的染色質結構,進而抑制轉錄。我們將從三個方向來驗證這個假說:

    方向(目標)一:決定組蛋白去乙醯化對於 ZFP42 轉錄抑制功能的影響
    方向(目標)二:決定組蛋白甲基化對於 ZFP42 轉錄抑制功能的影響
    方向(目標)三:決定聚腺核甘二磷酸聚合修飾作用對於 ZFP42 轉錄抑制功能的
    影響
    ZFP42 is a zinc-finger protein of the Krüpple-like factor (KLF) family known as a markerfor the embryonic lineage during development. However, the function of ZFP42 is almost
    completely unknown. Previously we demonstrated that ZFP42 is a transcriptional repressor.We now have preliminary results suggesting that ZFP42 represses transcription from the immunoglobulin κ light chain enhancer and interacts with histone deacetylases, a histonemethyltransferase, and a poly(ADP-ribose) polymerase. It has been shown that histonedeacetylation, histone methylation of specific lysine residues, and poly(ADP-ribosyl)ation
    status of histones as well as transcription factors all contribute to the establishment of a closedchromatin structure and hence transcriptional repression. In this proposed study, we would
    like to explore the mechanism of transcription repression of ZFP42 from a molecular level. I hypothesize that ZFP42 represses transcription through interacting with chromatin-modifying
    proteins, thereby creating a local environment favorable for repression. The following three aims will be executed to test this hypothesis:

    Aim 1. to determine the functional relationship between histone deacetylation and ZFP42-mediated transcriptional repression
    Aim 2. to determine the functional relationship between histone methylation and ZFP42-mediated transcriptional repression
    Aim 3. to determine the functional relationship between poly(ADP-ribosyl)ation and ZFP42-mediated transcriptional repression
    Appears in Collections:[生物科技學系] 科技部研究計畫

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