# Histone Nuclear Import and Beyond: Multifunctional Roles of Importins

## TL;DR

This paper reviews how importins help transport and stabilize histones during nuclear import, playing a key role in chromatin homeostasis.

## Contribution

The paper highlights the dual role of importins as both transporters and chaperones for histones, revealing their multifunctional roles in chromatin regulation.

## Key findings

- Importin-4/Kap123 acts as a transporter and chaperone for H3–H4 heterodimers with ASF1.
- Importin-9/Kap114 imports H2A–H2B heterodimers in a RanGTP-insensitive manner with Nap1.
- Importin-β/7 heterodimer facilitates linker histone H1 import through a newly clarified mechanism.

## 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.

Efficient nuclear import of histones requires coordinated action between histone chaperones and nuclear import receptors. Importin‐4, Importin‐9, and Importin‐β/7 not only transport specific histone complexes but also act as chaperones, stabilizing histones and ensuring their protected delivery for nucleosome assembly, highlighting importins as central regulators of chromatin homeostasis.