表觀遺傳學

表觀遺傳機制
表觀遺傳學已成為從事癌症、神經退化性疾病及成癮研究之科學家們不可或缺的關注領域。表觀遺傳機制涉及暫時性地激活或抑制基因表達。值得注意的是,儘管這些變化並未永久改變 DNA 序列,卻能代代相傳。表觀遺傳學的三大主要機制分別為 DNA 甲基化、組蛋白修飾及 RNA 調控。
精選類別
DNA 甲基化
DNA 甲基化是表觀遺傳學中最廣為人知的機制。該過程通常涉及一種甲基轉移酶,該酶協助將甲基基團添加至胞嘧啶(C)的第五位(C5)。此甲基化主要發生在胞嘧啶-磷酸-鳥嘌呤(CpG)二核苷酸上。然而,非 CpG 甲基化現象亦會發生。 DNA 甲基化分析常被用於協助理解基因表達。此類分析的例子包括:透過 DNA 消化進行甲基化定量,隨後利用高效液相層析(HPLC)或質譜分析;或是採用亞硫酸氫鈉轉化,接著進行 PCR 定序與分析。
組蛋白修飾
組蛋白修飾是另一種經典的表觀遺傳機制。它涉及透過乙醯化、甲基化、磷酸化及其他影響基因表達的機制,以多種方式改變組蛋白。 組蛋白是蛋白質,與DNA共同構成核小體。核小體的聚合體形成染色質,進而構成染色體。一般而言,組蛋白修飾發生在組蛋白N端尾部,該處含有高比例的賴胺酸或精胺酸。研究此種表觀遺傳調控的一種方法是透過染色質免疫沉澱(ChIP)實驗。
RNA 調控
相較於其他表觀遺傳機制,目前對 RNA 調控的了解尚不充分。一般認為,RNA 訊號傳導是透過調節染色質結構而在表觀遺傳中發揮作用。 研究人員正致力於探究 mRNA,特別是長非編碼 RNA 和微 RNA 等非編碼 RNA,如何調控基因表達。此外,可透過「RNA 純化法分離染色質」(ChIRP)或「RNA 免疫沉澱」(RIP)實驗,來釐清染色質與 RNA 之間的關係,以及 RNA 在表觀遺傳學中所扮演的角色。
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相關協定
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