The packaging of DNA into chromatin in eukaryotes regulates gene transcription, DNA replication and DNA repair. ATP-dependent chromatin remodelling enzymes (re)arrange nucleosomes at the first level of chromatin organization. Their Snf2-type motor ATPases alter histone–DNA interactions through a common DNA translocation mechanism. Whether remodeller activities mainly catalyse nucleosome dynamics or accurately co-determine nucleosome organization remained unclear. In this Review, we discuss the emerging mechanisms of chromatin remodelling: dynamic remodeller architectures and their interactions, the inner workings of the ATPase cycle, allosteric regulation and pathological dysregulation. Recent mechanistic insights argue for a decisive role of remodellers in the energy-driven self-organization of chromatin, which enables both stability and plasticity of genome regulation — for example, during development and stress. Different remodellers, such as members of the SWI/SNF, ISWI, CHD and INO80 families, process (epi)genetic information through specific mechanisms into distinct functional outputs. Combinatorial assembly of remodellers and their interplay with histone modifications, histone variants, DNA sequence or DNA-bound transcription factors regulate nucleosome mobilization or eviction or histone exchange. Such input–output relationships determine specific nucleosome positions and compositions with distinct DNA accessibilities and mediate differential genome regulation. Finally, remodeller genes are often mutated in diseases characterized by genome dysregulation, notably in cancer, and we discuss their physiological relevance.

在真核生物中，DNA 包装到染色质中可调节基因转录、DNA 复制和 DNA 修复。ATP 依赖性染色质重塑酶在染色质组织的第一级（重新）排列核小体。它们的 Snf2 型运动 ATP 酶通过常见的 DNA 易位机制改变组蛋白-DNA 相互作用。重塑活性是否主要催化核小体动力学或准确地共同决定核小体组织仍不清楚。在这篇综述中，我们讨论了染色质重塑的新兴机制：动态重塑架构及其相互作用、ATP 酶循环的内部运作、变构调节和病理失调。最近的机制见解认为，重塑者在能量驱动的染色质自组织中发挥着决定性作用，这使得基因组调控的稳定性和可塑性得以实现——例如，在发育和应激过程中。不同的重塑者，例如 SWI/SNF、ISWI、CHD 和 INO80 家族的成员，通过特定机制将（表观）遗传信息处理成不同的功能输出。重塑剂的组合组装及其与组蛋白修饰、组蛋白变体、DNA 序列或 DNA 结合转录因子的相互作用调节核小体动员或驱逐或组蛋白交换。这种输入-输出关系决定了具有不同DNA可及性的特定核小体位置和组成，并介导差异基因组调控。最后，重塑基因通常在以基因组失调为特征的疾病中发生突变，特别是在癌症中，我们讨论了它们的生理相关性。