Wolffe A P, Guschin D
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, NIH, Building 18T, Room 106, Bethesda, Maryland, 20892-5431, USA.
J Struct Biol. 2000 Apr;129(2-3):102-22. doi: 10.1006/jsbi.2000.4217.
The nucleosome and chromatin fiber provide the common structural framework for transcriptional control in eukaryotes. The folding of DNA within these structures can both promote and impede transcription dependent on structural context. Importantly, neither the nucleosome nor the chromatin fiber is a static structure. Histone dissociation, histone modification, nucleosome mobility, and assorted allosteric transitions contribute to transcriptional control. Chromatin remodeling is associated with gene activation and repression. Energy-dependent processes mediate the assembly of both activating and repressive proteins into the nucleosomal infrastructure. Recent progress allows the structural consequences of these processes to be visualized at the chromosomal level. DNA and RNA polymerase, SWI/SNF complexes, histone deacetylases, and acetyltransferases are targeted by gene-specific regulators to mediate these structural transitions. The mistargeting of these enzymes contributes to human developmental abnormalities and tumorigenesis. These observations illuminate the roles of chromatin and chromosomal structural biology in human disease.
核小体和染色质纤维为真核生物的转录调控提供了共同的结构框架。这些结构中DNA的折叠根据结构背景既可以促进也可以阻碍转录。重要的是,核小体和染色质纤维都不是静态结构。组蛋白解离、组蛋白修饰、核小体移动性以及各种变构转变都有助于转录调控。染色质重塑与基因激活和抑制相关。能量依赖过程介导激活蛋白和抑制蛋白组装到核小体结构中。最近的进展使得这些过程的结构后果能够在染色体水平上可视化。DNA和RNA聚合酶、SWI/SNF复合物、组蛋白脱乙酰酶和乙酰转移酶被基因特异性调节因子靶向,以介导这些结构转变。这些酶的错误靶向导致人类发育异常和肿瘤发生。这些观察结果阐明了染色质和染色体结构生物学在人类疾病中的作用。