Molecular population dynamics of DNA structures in a bcl-2 promoter sequence is regulated by small molecules and the transcription factor hnRNP LL.
Molecular population dynamics of DNA structures in a bcl-2 promoter sequence is regulated by small molecules and the transcription factor hnRNP LL.
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DOI：
10.1093/nar/gku185
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发表时间：
2014-05
影响因子：
14.9
通讯作者：
Mao H
中科院分区：
文献类型：
--
作者：
Cui Y;Koirala D;Kang H;Dhakal S;Yangyuoru P;Hurley LH;Mao H
寡核苷酸序列中不同结构之间展开自由能变化的微小差异可能导致复杂的种群平衡，这对系综技术的破译相当具有挑战性。在这里，我们引入了一种新的方法--分子布居动力学(MPD)来描述非B脱氧核糖核酸(DNA)结构之间的复杂平衡。利用激光镊子的机械展开，我们在一个富含胞嘧啶(C)的bcl2启动子序列中鉴定了六种DNA物种。比较了有和没有小分子(IMC-76或IMC-48)或转录因子hnRNP LL的这些物种的种群模式，以揭示不同物种的MPD。通过模式识别算法，我们发现IMC-48与hnRNP LL在稳定I-基序方面有80%的相似性，与60个S孵育的I-基序有80%的相似性。相比之下，IMC-76表现出相反的行为，更喜欢灵活的DNA发夹。在12 0-180 S孵育下，IMC-48和hnRNP LL破坏I基序的稳定，而I基序是先前被认为激活bcl2转录的。这些结果从群体平衡的角度提供了强有力的支持，即小分子和hnRNP LL可以通过与I基序相互作用来调控bcl2的转录。与生化结果的良好一致性有力地验证了MPD分析，我们预计它可以广泛应用于研究生物大分子的复杂平衡。
Minute difference in free energy change of unfolding among structures in an oligonucleotide sequence can lead to a complex population equilibrium, which is rather challenging for ensemble techniques to decipher. Herein, we introduce a new method, molecular population dynamics (MPD), to describe the intricate equilibrium among non-B deoxyribonucleic acid (DNA) structures. Using mechanical unfolding in laser tweezers, we identified six DNA species in a cytosine (C)-rich bcl-2 promoter sequence. Population patterns of these species with and without a small molecule (IMC-76 or IMC-48) or the transcription factor hnRNP LL are compared to reveal the MPD of different species. With a pattern recognition algorithm, we found that IMC-48 and hnRNP LL share 80% similarity in stabilizing i-motifs with 60 s incubation. In contrast, IMC-76 demonstrates an opposite behavior, preferring flexible DNA hairpins. With 120–180 s incubation, IMC-48 and hnRNP LL destabilize i-motifs, which has been previously proposed to activate bcl-2 transcriptions. These results provide strong support, from the population equilibrium perspective, that small molecules and hnRNP LL can modulate bcl-2 transcription through interaction with i-motifs. The excellent agreement with biochemical results firmly validates the MPD analyses, which, we expect, can be widely applicable to investigate complex equilibrium of biomacromolecules.
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转录依赖性动态超串联是一种短距离基因组力。
影响因子：
16.8
作者：
Kouzine, Fedor;Gupta, Ashutosh;Baranello, Laura;Wojtowicz, Damian;Ben-Aissa, Khadija;Liu, Juhong;Przytycka, Teresa M.;Levens, David
通讯作者：
Levens, David
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3.7
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Dhakal S;Lafontaine JL;Yu Z;Koirala D;Mao H
通讯作者：
Mao H
DOI：
10.1073/pnas.0506144102
发表时间：
2005-12-27
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
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影响因子：
8.4
作者：
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