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Histone Nuclear Import and Beyond: Multifunctional Roles of Importins.

Created on 10 Sep 2026

Authors

Natalia Bernardes, Yuh Min Chook

Published in

BioEssays : news and reviews in molecular, cellular and developmental biology. Volume 48. Issue 2. Pages e70119.

Abstract

The separation of DNA-based processes from cytoplasmic protein synthesis demands precise and effective nuclear import of histones and chromatin regulators. Because histones are highly basic and aggregation-prone, their proper folding, sequestration, and deposition into chromatin depend on coordinated action of histone chaperones and nuclear import receptors. This review summarizes recent advances in understanding the mechanisms of core and linker histone import and chaperoning. Structural and biochemical studies have elucidated how Importin-4/Kap123 mediates nuclear import of H3-H4 heterodimers in concert with ASF1, revealing Importin-4's dual role as both transporter and histone chaperone. Likewise, Importin-9/Kap114 recognizes and imports H2A-H2B heterodimers through a mechanism unusually insensitive to RanGTP, which cooperates with Nap1 for histone release. Finally, new structural analyses of the Importin-β-Importin-7 heterodimer clarify its mode of linker histone H1 import. Together, these studies establish importins as multifunctional factors that couple histone stabilization, protection from aberrant interactions, nuclear import, and targeted delivery for nucleosome assembly. Outstanding questions include how secondary importins, histone modifications, and compartment-specific chaperone dynamics regulate histone trafficking, and whether importins themselves function in nucleosome assembly. Addressing these questions will define how nuclear import integrates with chromatin homeostasis.

PMID:
41736444
Bibliographic data and abstract were imported from PubMed on 10 Sep 2026.

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