Department of Medicine, Division of Human Genetics, University of Washington, Seattle, WA 98195, USA.
Annu Rev Genomics Hum Genet. 2012;13:59-82. doi: 10.1146/annurev-genom-090711-163818. Epub 2012 Jun 6.
Eukaryotic genomic DNA is combined with histones, nonhistone proteins, and RNA to form chromatin, which is extensively packaged hierarchically to fit inside a cell's nucleus. The nucleosome-comprising a histone octamer with 147 base pairs of DNA wrapped around it-is the initial level and the repeating unit of chromatin packaging, which electron microscopy first made visible to the human eye as "beads on a string" nearly four decades ago. The mechanism and nature of chromatin packaging are still under intense research. Recently, classic methods like chromatin immunoprecipitation and digestion with deoxyribonuclease and micrococcal nuclease have been combined with high-throughput sequencing to provide detailed nucleosome occupancy maps, and chromosome conformation capture and its variants have revealed that higher-order chromatin structure involves long-range loop formation between distant genomic elements. This review discusses the methods for identifying higher-order chromatin structure and the information they have provided on this important topic.
真核生物基因组 DNA 与组蛋白、非组蛋白和 RNA 结合形成染色质，染色质经过广泛的层次化包装以适应细胞内的细胞核。核小体——由一个包含 147 个碱基对 DNA 的组蛋白八聚体组成，是染色质包装的初始水平和重复单元，近四十年前电子显微镜首次将其可视化为人眼所见的“串珠”。染色质包装的机制和性质仍在深入研究中。最近，经典方法如染色质免疫沉淀和脱氧核糖核酸酶及微球菌核酸酶消化已与高通量测序相结合，提供了详细的核小体占有率图谱，而染色质构象捕获及其变体揭示了高级染色质结构涉及远距离基因组元件之间的长距离环形成。本文讨论了鉴定高级染色质结构的方法及其在这一重要主题上提供的信息。
