A transient ischemic environment induces reversible compaction of chromatin.
A transient ischemic environment induces reversible compaction of chromatin.
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DOI：
10.1186/s13059-015-0802-2
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发表时间：
2015-11-05
期刊：
影响因子：
12.3
通讯作者：
Reid G
中科院分区：
文献类型：
--
作者：
Kirmes I;Szczurek A;Prakash K;Charapitsa I;Heiser C;Musheev M;Schock F;Fornalczyk K;Ma D;Birk U;Cremer C;Reid G
细胞通过即时的转录、翻译和代谢反应来检测和适应低氧和营养应激。用DNA结合染料和乙酰化组蛋白的单分子定位显微镜、染色质对DNAseI消化的敏感性以及核心和连接子组蛋白的光漂白后荧光恢复(FRAP)研究了缺血对染色质纳米结构的环境影响。心肌细胞系HL-1短期的缺氧和营养剥夺导致了一种以前未描述的染色质结构，由大的、染色质稀疏的空洞组成，散布在DNA致密的中空螺旋结构之间，尺寸为40-700 nm。染色质的压缩是可逆的，在恢复常氧和营养后，染色质瞬时采用比未处理细胞更开放的结构。染色质的紧凑状态减少了转录，而恢复时诱导的开放染色质结构刺激了转录的一过性增加。用DNAseI消化染色质证实，缺乏氧气和营养会导致染色质紧凑。染色质紧凑与三磷酸腺苷的耗尽和多胺库重新分布到细胞核中有关。FRAP证明核心组蛋白不会从致密的染色质中取代；然而，连接子组蛋白H1的流动性显著降低，其程度远远超过异染色质和常染色质之间组蛋白H1流动性的差异。这些研究展示了染色质结构对环境条件做出物理反应的动态能力，直接将细胞能量状态与染色质紧凑联系起来，并为了解缺血对细胞核结构的影响提供了洞察力。本文的在线版本(doi：10.1186/s13059-0150802-2)包含补充材料，授权用户可以使用。
Cells detect and adapt to hypoxic and nutritional stress through immediate transcriptional, translational and metabolic responses. The environmental effects of ischemia on chromatin nanostructure were investigated using single molecule localization microscopy of DNA binding dyes and of acetylated histones, by the sensitivity of chromatin to digestion with DNAseI, and by fluorescence recovery after photobleaching (FRAP) of core and linker histones. Short-term oxygen and nutrient deprivation of the cardiomyocyte cell line HL-1 induces a previously undescribed chromatin architecture, consisting of large, chromatin-sparse voids interspersed between DNA-dense hollow helicoid structures 40–700 nm in dimension. The chromatin compaction is reversible, and upon restitution of normoxia and nutrients, chromatin transiently adopts a more open structure than in untreated cells. The compacted state of chromatin reduces transcription, while the open chromatin structure induced upon recovery provokes a transitory increase in transcription. Digestion of chromatin with DNAseI confirms that oxygen and nutrient deprivation induces compaction of chromatin. Chromatin compaction is associated with depletion of ATP and redistribution of the polyamine pool into the nucleus. FRAP demonstrates that core histones are not displaced from compacted chromatin; however, the mobility of linker histone H1 is considerably reduced, to an extent that far exceeds the difference in histone H1 mobility between heterochromatin and euchromatin. These studies exemplify the dynamic capacity of chromatin architecture to physically respond to environmental conditions, directly link cellular energy status to chromatin compaction and provide insight into the effect ischemia has on the nuclear architecture of cells. The online version of this article (doi:10.1186/s13059-015-0802-2) contains supplementary material, which is available to authorized users.