Acetylation Mimics Within a Single Nucleosome Alter Local DNA Accessibility In Compacted Nucleosome Arrays.
Acetylation Mimics Within a Single Nucleosome Alter Local DNA Accessibility In Compacted Nucleosome Arrays.
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乙酰化模拟物中的单个核小体改变了压实核小体阵列中局部DNA的可及性。
DOI：
10.1038/srep34808
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发表时间：
2016-10-06
影响因子：
4.6
通讯作者：
Hayes JJ
中科院分区：
文献类型：
--
作者：
Mishra LN;Pepenella S;Rogge R;Hansen JC;Hayes JJ
沉默基因位点的激活被认为涉及开创性转录因子，其启动局部染色质结构的变化以增加启动子可及性和下游效应子的结合。为了更好地理解基因座激活的第一步的分子要求，我们研究了单个核小体的乙酰化是否足以改变浓缩的25-核小体阵列内的DNA可及性。我们发现组蛋白H4尾部结构域内的乙酰化模拟物增加了周围接头DNA的可接近性，增加的可接近性定位于修饰的核小体的紧邻处。相反，H3尾内的乙酰化模拟物几乎没有影响，但能够与H4尾乙酰化模拟物协同作用以进一步增加可及性。此外，用无核小体区域替换中央核小体也导致局部而非全局DNA可及性增加。我们的研究结果表明，修改或破坏只有一个单一的目标核小体的结果显着的变化，在当地的染色质结构，并建议非常本地化的染色质修饰赋予先锋转录因子足以启动级联的事件，导致启动子激活。
The activation of a silent gene locus is thought to involve pioneering transcription factors that initiate changes in the local chromatin structure to increase promoter accessibility and binding of downstream effectors. To better understand the molecular requirements for the first steps of locus activation, we investigated whether acetylation of a single nucleosome is sufficient to alter DNA accessibility within a condensed 25-nucleosome array. We found that acetylation mimics within the histone H4 tail domain increased accessibility of the surrounding linker DNA, with the increased accessibility localized to the immediate vicinity of the modified nucleosome. In contrast, acetylation mimics within the H3 tail had little effect, but were able to synergize with H4 tail acetylation mimics to further increase accessibility. Moreover, replacement of the central nucleosome with a nucleosome free region also resulted in increased local, but not global DNA accessibility. Our results indicate that modification or disruption of only a single target nucleosome results in significant changes in local chromatin architecture and suggest that very localized chromatin modifications imparted by pioneer transcription factors are sufficient to initiate a cascade of events leading to promoter activation.
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影响因子：
10.5
作者：
Iwafuchi-Doi M;Zaret KS
通讯作者：
Zaret KS
影响因子：
4.8
作者：
Pepenella, Sharon;Murphy, Kevin J.;Hayes, Jeffrey J.
通讯作者：
Hayes, Jeffrey J.
影响因子：
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作者：
Hayes, JJ;Lee, KM
通讯作者：
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作者：
Kan, Pu-Yeh;Caterino, Tamara L.;Hayes, Jeffrey J.
通讯作者：
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作者：
Anderson, JD;Lowary, PT;Widom, J
通讯作者：
Widom, J