RG Development & Disease, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Institute for Medical and Human Genetics, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany; Charité - Universitätsmedizin Berlin, BCRT - Berlin Institute of Health Center for Regenerative Therapies, 10178 Berlin, Germany.
Curr Opin Genet Dev. 2020 Apr;61:1-8. doi: 10.1016/j.gde.2020.02.015. Epub 2020 Mar 19.
The causal relationship between 3D chromatin domains and gene regulation has been of considerable debate in recent years. Initial Hi-C studies profiling the 3D chromatin structure of the genome described evolutionarily conserved Topologically Associating Domains (TADs) that correlated with gene expression. Subsequent evidence from mouse models and human disease directly linked TADs to gene regulation. However, a number of focused genetic and genome-wide studies questioned the relevance of 3D chromatin domains for orchestrating gene expression, ultimately yielding a more multi-layered view of 3D chromatin structure and gene regulation. We review the evidence for and against the importance of 3D chromatin structure for gene regulation and argue for a more comprehensive classification of regulatory chromatin domains that integrates 3D chromatin structure with genomic, functional, and evolutionary conservation.
近年来，三维染色质结构域与基因调控之间的因果关系一直备受争议。最初的 Hi-C 研究对基因组的三维染色质结构进行了描述，发现了与基因表达相关的进化保守的拓扑关联结构域（TADs）。随后，来自小鼠模型和人类疾病的证据直接将 TADs 与基因调控联系起来。然而，一些有针对性的遗传和全基因组研究对三维染色质结构域在调控基因表达方面的相关性提出了质疑，最终对三维染色质结构和基因调控产生了更为多层次的认识。我们综述了三维染色质结构对基因调控重要性的证据，并主张更全面的调控染色质结构域分类，将三维染色质结构与基因组、功能和进化保守性相结合。
