發表在BioMed Central開放期刊Cell & Bioscience 上的新研究,首次說明了左旋型的Z型DNA,它通常只被發現於DNA被複製的地方,也能在核小體上形成。
提供生命藍圖的DNA結構曾被描述為一個雙螺旋。為了節省細胞核內空間,DNA緊緊地纏繞形成核小體的蛋白質,然後進一步纏繞,壓縮成染色質,接著壓縮成染色體。但是,右手螺旋(也稱為B型DNA)的這種熟悉形象不是DNA的唯一形式。在DNA被複製成RNA的位置(用作製造蛋白質指令的信使),DNA需要解纏繞,在負超螺旋過程中,能形成DNA雙螺旋的左手螺旋變體(Z-DNA)。
最開始認為,Z-DNA只能在活性RNA聚合酶(組裝RNA的酶)存在下形成。但是,最近發現,SWI/SNF能將某些B-DNA序列轉換成Z-DNA,其中SWI/SNF是一種參與重塑核小體和允許RNA聚合酶接近DNA的蛋白質。
由Keji Zhao博士領導的研究小組發現,他們通過增加SWI/SNF 和 ATP(細胞能量來源)能將核小體上的B-DNA轉換成Z-DNA,形成的Z-核小體是一種新結構。
來自美國國立衛生研究院的趙博士解釋說,"事實上,我們在核小體上發現Z-DNA的事實是理解染色體重組與Z-DNA調節基因表達的作用的新一步。然而,Z-核小體很可能是一個暫時結構,但它為DNA結合蛋白配置提供了一個機會的窗口,這可以招募、調節或阻止轉錄機制和蛋白表達。"(生物谷bioon.com)
SWI/SNF-mediated chromatin remodeling induces Z-DNA formation on a nucleosome
Niveen Mulholland, Yan Xu, Hiroshi Sugiyama, Keji Zhao
Abstract Background Z-DNA is a higher-energy, left-handed form of the double helix. A primary function of Z-DNA formation is to facilitate transcriptional initiation and activation. Sequences favoring Z-DNA formation are frequently located in promoter regions and Z-DNA is stabilized by torsional strain resulting from negative supercoiling, such as that generated by an actively transcribing polymerase or by a nucleosome remodeling event. We previously have shown that activation of the CSF1 gene by a chromatin remodeling event in the promoter results in Z-DNA formation at TG repeats within the promoter. Results We show that remodeling of a mononucleosome by the human SWI/SNF complex results in Z-DNA formation when the DNA within the mononucleosome contains Z-DNA favoring sequence. Nuclease accessibility patterns of nucleosome core particle consisting of Z-DNA are quite different from counterpart nucleosomes containing classic B-DNA. Z-nucleosomes represent a novel mononucleosome structure. Conclusions: We present evidence that Z-DNA can form on nucleosomes though previous observations indicate the occlusion of nucleosome formation from Z-DNA.