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.

中文翻译：

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3D染色质结构域在基因调控中的作用：关于基因组组织的多方面观点。

近年来，3D染色质结构域与基因调控之间的因果关系引起了广泛的争论。最初的Hi-C研究对基因组的3D染色质结构进行了分析，描述了与基因表达相关的进化保守的拓扑关联域（TAD）。小鼠模型和人类疾病的后续证据将TAD与基因调控直接相关。然而，许多集中的遗传和全基因组研究对3D染色质域与协调基因表达的相关性提出了质疑，最终产生了3D染色质结构和基因调控的更多层视图。