nucleosomepositioners

Nucleosome positioners are factors that influence where nucleosomes are located and how they move along chromatin. Nucleosomes, the basic units of chromatin, consist of DNA wrapped around histone octamers and play a key role in regulating access to the genome. Positioning is governed by both intrinsic DNA properties and active enzymatic processes.

Two broad modes shape nucleosome positions. First, intrinsic or sequence-driven positioning arises from the physical properties of DNA, which can favor or disfavor wrapping around histones and create preferred nucleosome occupancies in certain regions. Second, active repositioning occurs when ATP-dependent chromatin remodeling complexes slide nucleosomes along DNA, eject them, or exchange histone variants, thereby altering accessibility.

Major families of chromatin remodelers include SWI/SNF, ISWI, CHD, and INO80. ISWI and related factors tend to space nucleosomes regularly and organize higher-order arrays, while SWI/SNF complexes often slide or evict nucleosomes to expose regulatory elements. CHD remodelers participate in nucleosome assembly and spacing, and INO80 complexes can exchange histone variants and assist in DNA repair. Remodelers often function with histone chaperones and variant histones (for example H2A.Z and H3.3) to fine-tune chromatin structure.

Nucleosome positioning has direct consequences for gene regulation. Regions surrounding promoters and enhancers commonly exhibit nucleosome-depleted regions, enabling transcription factor binding, while positioned nucleosomes can repress or facilitate transcription depending on context. Misregulation of remodelers is linked to development defects and diseases, including cancer.

Experimental approaches to study positioners include MNase-seq, ATAC-seq, and chemical mapping, which reveal nucleosome occupancy and dynamics, as well as assays that track remodeling activity in vitro and in vivo.