Transcriptional activation by mitochondrial transcription factor A involves preferential distortion of promoter DNA.
Transcriptional activation by mitochondrial transcription factor A involves preferential distortion of promoter DNA.
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DOI：
10.1093/nar/gkr787
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发表时间：
2012-01
影响因子：
14.9
通讯作者：
Churchill ME
中科院分区：
文献类型：
--
作者：
Malarkey CS;Bestwick M;Kuhlwilm JE;Shadel GS;Churchill ME
线粒体转录因子A（mtTFA/TFAM）是核编码的高迁移率族盒（HMG盒）蛋白，其通过特异性识别轻链和重链启动子（LSP、HSP 1）来调节线粒体基因组的转录。TFAM还以非序列特异性（NSS）方式结合线粒体DNA，并促进其包装成类核结构。然而，这两种不同的结合模式的DNA弯曲的要求和贡献还没有得到详细解决，这促使TFAM对启动子和非启动子DNA的结合和弯曲性质的比较。启动子DNA比非启动子DNA更大程度地增加TFAM的稳定性。然而，TFAM与启动子和非特异性（NS）DNA的DNA结合的热力学性质彼此相似，并与其他NSS HMG盒蛋白相似。荧光共振能量转移分析表明，TFAM弯曲启动子DNA的程度比NS DNA。与此相反，TFAM缺乏C-末端尾巴扭曲启动子和非启动子DNA的显着降低的程度，相应的显着降低体外LSP和HSP 1的转录激活能力。因此，由C-末端尾赋予的启动子DNA的增强的弯曲是TFAM通过核心线粒体转录机器激活启动子特异性起始的能力的关键组成部分。
Mitochondrial transcription factor A (mtTFA/TFAM) is a nucleus-encoded, high-mobility-group-box (HMG-box) protein that regulates transcription of the mitochondrial genome by specifically recognizing light-strand and heavy-strand promoters (LSP, HSP1). TFAM also binds mitochondrial DNA in a non-sequence specific (NSS) fashion and facilitates its packaging into nucleoid structures. However, the requirement and contribution of DNA-bending for these two different binding modes has not been addressed in detail, which prompted this comparison of binding and bending properties of TFAM on promoter and non-promoter DNA. Promoter DNA increased the stability of TFAM to a greater degree than non-promoter DNA. However, the thermodynamic properties of DNA binding for TFAM with promoter and non-specific (NS) DNA were similar to each other and to other NSS HMG-box proteins. Fluorescence resonance energy transfer assays showed that TFAM bends promoter DNA to a greater degree than NS DNA. In contrast, TFAM lacking the C-terminal tail distorted both promoter and non-promoter DNA to a significantly reduced degree, corresponding with markedly decreased transcriptional activation capacity at LSP and HSP1 in vitro. Thus, the enhanced bending of promoter DNA imparted by the C-terminal tail is a critical component of the ability of TFAM to activate promoter-specific initiation by the core mitochondrial transcription machinery.
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