最新一期Molecular Cell雜志上，美國密歇根大學副教授竇雅麗小組發(fā)表了有關(guān)MOF的研究成果,，提出了一種新型的調(diào)控機制,。
MYST組蛋白乙酰轉(zhuǎn)移酶（histone acetyltransferase, HAT）廣泛存在于從酵母到人的真核生物中，在真核生物的轉(zhuǎn)錄調(diào)控中起著重要的作用,，這一家族中MOF蛋白在轉(zhuǎn)錄活性中扮演著重要的角色——組蛋白H4乙酰轉(zhuǎn)移至K16,。MOF基因長1575bp(GenBank登錄號為DQ442997)，開放閱讀框(ORF)長1326bp,，無內(nèi)含子,，基因編碼442個氨基酸，預測蛋白質(zhì)的分子量為51.4kD,，序列中有HAT核心結(jié)構(gòu)域,、鋅指結(jié)構(gòu)域和染色質(zhì)域3個保守的結(jié)構(gòu)域，與其他物種同源基因具有較高的序列相似性,。
到目前為止,，雖然已經(jīng)獲得了一些MOF調(diào)控方面的研究成果，但是在高等真核生物中,，科學家們還不是很清楚MOF的調(diào)控機制和模式,。在這篇文章中，研究人員在兩組進化上保守的不同復合物：MSL和MOF-MSL1v1中分析MOF的乙酰轉(zhuǎn)移酶活性,。
他們發(fā)現(xiàn)雖然這兩種MOF復合物在組蛋白H4K16的活性方面存在較小差異,，但是在對底物p53這種非組蛋白的作用活性方面卻存在極大差異。進一步研究證明MOF-MSF 1v1是一種無論體內(nèi),，還是體外實驗中,，p53靶基因獲得最佳轉(zhuǎn)錄活性的必需因子，這些研究結(jié)果提出了一種新型的作用模型：兩個MOF復合物能與其它組蛋白修飾活性因子一起調(diào)控轉(zhuǎn)錄活性的不同階段,。(生物谷Bioon.com)
生物谷推薦原始出處：
Molecular Cell,23 October 2009 doi:10.1016/j.molcel.2009.07.031
Two Mammalian MOF Complexes Regulate Transcription Activation by Distinct Mechanisms
Xiangzhi Li1, Lipeng Wu1, Callie Ann Sprunger Corsa1, Steve Kunkel1 and Yali Dou1, 2, ,
1 Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA
2 Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
In mammals, MYST family histone acetyltransferase MOF plays important roles in transcription activation by acetylating histone H4 on K16, a prevalent mark associated with chromatin decondensation, and transcription factor p53 on K120, which is important for activation of proapoptotic genes. However, little is known about MOF regulation in higher eukaryotes. Here, we report that the acetyltransferase activity of MOF is tightly regulated in two different but evolutionarily conserved complexes, MSL and MOF-MSL1v1. Importantly, we demonstrate that while the two MOF complexes have indistinguishable activity on histone H4 K16, they differ dramatically in acetylating nonhistone substrate p53. We further demonstrate that MOF-MSL1v1 is specifically required for optimal transcription activation of p53 target genes both in vitro and in vivo. Our results support a model that these two MOF complexes regulate distinct stages of transcription activation in cooperation with other histone modifying activities.
