Radial chromatin positioning is shaped by local gene density, not by gene expression.
Radial chromatin positioning is shaped by local gene density, not by gene expression.
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DOI：
10.1007/s00412-007-0098-4
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发表时间：
2007-06
期刊：
影响因子：
1.6
通讯作者：
Cremer M
中科院分区：
文献类型：
--
作者：
Küpper K;Kölbl A;Biener D;Dittrich S;von Hase J;Thormeyer T;Fiegler H;Carter NP;Speicher MR;Cremer T;Cremer M
中期染色体的G-带和r -带在基因密度、CG含量、复制时间和染色质致密性方面存在显著差异。基因密集的、转录活跃的、早期复制的染色质优先定位于核内部，而基因贫乏的、后期复制的染色质优先定位于核包膜，已被证明在各种细胞类型中具有进化保守性。然而，不同的局部染色质特征对染色质径向核排列的影响尚不清楚。特别是，尚不清楚径向染色质定位是否优先由局部基因密度本身或其他相关参数（如复制时间或转录活性）形成。线性脱氧核糖核酸（DNA）序列上这些不同的染色质特征的相互依赖关系阻碍了对这些参数的简单解剖，这些参数对于将线性DNA组织重组为核空间中观察到的不同径向染色质排列的重要性。为了分析这一问题，我们从HSA 11、12、18和19中收集细菌人工染色体（BAC）克隆，分别代表R/ g波段分配的染色质、不同基因密度的片段和不同表达水平的基因位点，构建了探针集。利用多色三维荧光原位杂交（FISH）和三维图像分析，我们确定了它们在细胞核中的定位以及它们在相应染色体区域内或外的位置（CT）。对于每个BAC数据，在2和10 mb窗口内的局部基因密度，以及GC（鸟嘌呤和胞嘧啶）含量，复制时间和表达水平被确定。这些参数与核定位的相关性分析显示，区域基因密度是决定核中染色质径向定位的决定性参数，而不是带分配、复制时间和转录活性。我们展示了相对于核边界的ct内基因密集与基因贫乏染色质的极化分布。虽然我们证实了先前的报道，即11p15.5上约2 Mb的特定基因密集和转录高活性区域经常从领土表面环出，但基因密集和高表达序列通常不会像之前所建议的那样优先出现在CT表面。
G- and R-bands of metaphase chromosomes are characterized by profound differences in gene density, CG content, replication timing, and chromatin compaction. The preferential localization of gene-dense, transcriptionally active, and early replicating chromatin in the nuclear interior and of gene-poor, later replicating chromatin at the nuclear envelope has been demonstrated to be evolutionary-conserved in various cell types. Yet, the impact of different local chromatin features on the radial nuclear arrangement of chromatin is still not well understood. In particular, it is not known whether radial chromatin positioning is preferentially shaped by local gene density per se or by other related parameters such as replication timing or transcriptional activity. The interdependence of these distinct chromatin features on the linear deoxyribonucleic acid (DNA) sequence precludes a simple dissection of these parameters with respect to their importance for the reorganization of the linear DNA organization into the distinct radial chromatin arrangements observed in the nuclear space. To analyze this problem, we generated probe sets of pooled bacterial artificial chromosome (BAC) clones from HSA 11, 12, 18, and 19 representing R/G-band-assigned chromatin, segments with different gene density and gene loci with different expression levels. Using multicolor 3D flourescent in situ hybridization (FISH) and 3D image analysis, we determined their localization in the nucleus and their positions within or outside the corresponding chromosome territory (CT). For each BAC data on local gene density within 2- and 10-Mb windows, as well as GC (guanine and cytosine) content, replication timing and expression levels were determined. A correlation analysis of these parameters with nuclear positioning revealed regional gene density as the decisive parameter determining the radial positioning of chromatin in the nucleus in contrast to band assignment, replication timing, and transcriptional activity. We demonstrate a polarized distribution of gene-dense vs gene-poor chromatin within CTs with respect to the nuclear border. Whereas we confirm previous reports that a particular gene-dense and transcriptionally highly active region of about 2 Mb on 11p15.5 often loops out from the territory surface, gene-dense and highly expressed sequences were not generally found preferentially at the CT surface as previously suggested.
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影响因子：
7.5
作者：
Cremer, Thomas;Cremer, Marion;Fakan, Stanislav
通讯作者：
Fakan, Stanislav
DOI：
10.1083/jcb.145.6.1119
发表时间：
1999-06-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Croft JA;Bridger JM;Boyle S;Perry P;Teague P;Bickmore WA
通讯作者：
Bickmore WA
影响因子：
3.5
作者：
Furey, TS;Haussler, D
通讯作者：
Haussler, D
影响因子：
7
作者：
Fiegler, Heike;Redon, Richard;Carter, Nigel P.
通讯作者：
Carter, Nigel P.
影响因子：
2.6
作者：
Cremer, M;von Hase, J;Cremer, T
通讯作者：
Cremer, T