%0 Journal Article
%T <br>
%A 刘思睿
%A 周瑞
%A 权慧
%A 杨立江
%A 田昊
%A 高毅勤
%J 物理化学学报
%D 2020
%R 10.3866/PKU.WHXB201907010
%X 染色质高级结构在基因调控中起到不可忽视的作用，染色质结构的形成与调控机制受到广泛关注。“相分离”理论近年来受到较多关注，异染色质与转录因子在其中的作用引人瞩目。但是，目前的相分离模型更关注结合因子与表观遗传性质，对DNA序列自身的作用理解尚较不充分。许多物种基因组的序列分布均具有多尺度的不均一性，仅基于CpG岛(CpG island，CGI)密度差异这一序列性质，就可以划分出基因、表观遗传、结构和转录性质都截然不同的高CGI密度“森林”和低CGI密度“草原”两种序列区域，体现了基因组自身的马赛克性。本文聚焦染色质结构的序列依赖性，讨论了染色质结构模型的研究进展，关注在序列几乎相同的不同细胞类型中的序列-结构关系及其功能调控，对发育、分化、衰老、疾病等多种过程的染色质结构变化进行了系统分析。针对基于序列的染色质相分离模型，对其物理驱动力进行了讨论，并在该模型的框架下基于相分离的物理特性，对温度、序列不均一性等物理因素对染色质结构可能造成的影响进行了探讨。<br>The high-order chromatin structure plays a non-negligible role in gene regulation. The formation of chromatin structure and its regulatory mechanisms have been studied intensely. To analyze the high-order chromatin structures, both computational and physical models have been developed, including polymer physics models and molecular crowding models. Over the past few years, the phase separation theory has drawn a lot of research interest, and the effect of heterochromatin and transcriptional factors (TFs) on phase separation has attracted much attention. Existing phase separation models for chromatin focus on multivalent molecules or on epigenetic properties and does not adequately explore the dependence of chromatin structure organization and remodeling on DNA sequence. Genomes of a number of species are highly uneven at multiple scales. It can be divided purely based on sequential properties into two sequentially, epigenetically, and transcriptionally distinct regions, namely forest and prairie domains, demonstrating the intrinsic mosaicity in genome. Compared to prairies, forest domains are on average more gene-rich, accessible, transcriptionally active, higher in open-sea methylation level, and are enriched in RNA polymerase Ⅱ binding sites as well as active histone modifications. Moreover, different structural properties of these two types of sequential domains suggest that sequence may play a role in topologically associated domain (TAD) and compartment formation. The chromatin sequence-structural relationship and functional regulation in different cell types with almost identical sequences are discussed in this review. We try to describe the evolution of chromatin structure in multiple biological processes including early development, differentiation, and senescence in a unified framework. The forest and prairie domains with high and low CGI densities, respectively, show enhanced segregation from each other in development, differentiation, and senescence. Meanwhile the multiscale forest-prairie spatial intermingling is cell-type specific and increases upon differentiation, thereby helping to define cell identity. The
%U http://www.whxb.pku.edu.cn/CN/Y2020/V36/I1/1907010