Teif Vladimir B, Rippe Karsten
Research Group Genome Organization & Function, Deutsches Krebsforschungszentrum and BioQuant, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Nucleic Acids Res. 2009 Sep;37(17):5641-55. doi: 10.1093/nar/gkp610. Epub 2009 Jul 22.
Nucleosome positions on the DNA are determined by the intrinsic affinities of histone proteins to a given DNA sequence and by the ATP-dependent activities of chromatin remodeling complexes that can translocate nucleosomes with respect to the DNA. Here, we report a theoretical approach that takes into account both contributions. In the theoretical analysis two types of experiments have been considered: in vitro experiments with a single reconstituted nucleosome and in vivo genome-scale mapping of nucleosome positions. The effect of chromatin remodelers was described by iteratively redistributing the nucleosomes according to certain rules until a new steady state was reached. Three major classes of remodeler activities were identified: (i) the establishment of a regular nucleosome spacing in the vicinity of a strong positioning signal acting as a boundary, (ii) the enrichment/depletion of nucleosomes through amplification of intrinsic DNA-sequence-encoded signals and (iii) the removal of nucleosomes from high-affinity binding sites. From an analysis of data for nucleosome positions in resting and activated human CD4(+) T cells [Schones et al., Cell 132, p. 887] it was concluded that the redistribution of a nucleosome map to a new state is greatly facilitated if the remodeler complex translocates the nucleosome with a preferred directionality.
核小体在DNA上的位置由组蛋白对特定DNA序列的内在亲和力以及染色质重塑复合物的ATP依赖活性决定，这些复合物能够使核小体相对于DNA发生移位。在此，我们报告一种兼顾这两种作用的理论方法。在理论分析中，考虑了两类实验：使用单个重组核小体的体外实验以及核小体位置的体内全基因组规模图谱。染色质重塑因子的作用通过根据特定规则反复重新分布核小体来描述，直到达到新的稳态。确定了三类主要的重塑因子活性：（i）在作为边界的强定位信号附近建立规则的核小体间距，（ii）通过放大内在DNA序列编码信号使核小体富集/耗尽，以及（iii）从高亲和力结合位点去除核小体。通过对静息和活化的人CD4(+) T细胞中核小体位置数据的分析[肖内斯等人，《细胞》132卷，第887页]得出结论，如果重塑复合物以优先的方向性移位核小体，核小体图谱重新分布到新状态会大大加快。
