Nuclear import of histones

Abstract

The transport of histones from the cytoplasm to the nucleus of the cell, through the nuclear membrane, is a cellular process that regulates the supply of new histones in the nucleus and is key for DNA replication and transcription. Nuclear import of histones is mediated by proteins of the karyopherin family of nuclear transport receptors. Karyopherins recognize their cargos through linear motifs known as nuclear localization/export sequences or through folded domains in the cargos. Karyopherins interact with nucleoporins, proteins that form the nuclear pore complex, to promote the translocation of their cargos into the nucleus. When binding to histones, karyopherins not only function as nuclear import receptors but also as chaperones, protecting histones from non-specific interactions in the cytoplasm, in the nuclear pore and possibly in the nucleus. Studies have also suggested that karyopherins might participate in histones deposition into nucleosomes. In this review we describe structural and biochemical studies from the last two decades on how karyopherins recognize and transport the core histone proteins H3, H4, H2A and H2B and the linker histone H1 from the cytoplasm to the nucleus, which karyopherin is the major nuclear import receptor for each of these histones, the oligomeric state of histones during nuclear import and the roles of post-translational modifications, histone-chaperones and RanGTP in regulating these nuclear import pathways.

T-cell receptor (TCR) signaling promotes the assembly of RanBP2/RanGAP1-SUMO1/Ubc9 nuclear pore subcomplex via PKC-θ-mediated phosphorylation of RanGAP1

“…To determine whether the nuclear transport defect resulting from PKC-θ deficiency is a generalized effect, we compared the nuclear transport of additional proteins in wild-type or PKC-θ knockdown Jurkat T cells (Figure 7). The proteins we tested were: RNA exosome complex subunit Dis3, ribosome subunits RPS3 and RPL26, tumor suppressor p53, histone H1, which are importin-β1-dependent; histones (H2B, H3), protein/RNA export receptor CRM1, which are Ran-dependent but importin-β1-independent; and Ran-independent mRNA export receptor NXF1 (Bernardes & Chook, 2020;Serpeloni, Vidal, Goldenberg, Avila, & Hoffmann, 2011).…”

What Are the Potential Roles of Nuclear Perlecan and Other Heparan Sulphate Proteoglycans in the Normal and Malignant Phenotype

“…The transport of histones from the cytoplasm to the nucleus of the cell, through the nuclear membrane, is a regulated cellular process required for the supply of new histones to the nucleus, essential for DNA replication and transcription [ 250 ]. Chromatin contains the core histone proteins H3, H4, H2A and H2B and the linker histone H1, which need to be transported from the cytoplasm into the nucleus [ 250 ]. Histones finetune the organisation and functional properties of chromatin [ 251 ].…”

Histone Chaperone Nrp1 Mutation Affects the Acetylation of H3K56 in Tetrahymena thermophila

“…The correct assembly and disassembly of nucleosomes are imperative for genome transcription, replication, and repair [1]. Histones H3 and H4 form the core of the nucleosome, while histones H2A and H2B bind at the periphery of the nucleosome [2]. Histone chaperones regulate histone assembly and disassembly [3], promote the interaction of new histones with other chaperones [4], mediate histone epigenetic modification [5], participate in ATP-dependent nucleosome remodeling [6], and regulate histone exchange during transcription [7].…”