Reference: Blackwell JS Jr, et al. (2007) Mutational analysis of H3 and H4 N termini reveals distinct roles in nuclear import. J Biol Chem 282(28):20142-50

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Abstract


Core histones H3 and H4 are rapidly imported into the nucleus by members of the karyopherin (Kap)/importin family. We showed that H3 and H4 interact with Kap123p, histone acetyltransferase-B complex (HAT-B), and Asf1p in cytosol. In vivo analysis indicated that Kap123p is required for H3-mediated import, whereas H4 utilizes multiple Kaps including Kap123p. The evolutionary conservation of H3 and H4 cytoplasmic acetylation led us to analyze the role of acetylation in nuclear transport. We determined that lysine 14 is critical for H3 NLS function in vivo and demonstrated that mutation of H3 lysine 14 to the acetylation-mimic glutamine decreased association with Kap123p in vitro. Several lysines in the H4 NLS are important for its function. We showed that mutation of key lysines to glutamine resulted in a greater import defect than mutation to arginine, suggesting that positive charge promotes NLS function. Lastly we determined that six of ten N-terminal acetylation sites in H3 and H4 can be mutated to arginine, indicating that deposition acetylation is not absolutely necessary in vivo. However, the growth defect of these mutants suggests that acetylation does play an important role in import. These findings suggest a model where cytosolic histones bind import karyopherins prior to acetylation. Other factors are recruited to this complex such as HAT-B and Asf1p; these factors in turn promote acetylation. Acetylation may be important for modulating the interaction with transport factors and may play a role in the release of histones from karyopherins in the nucleus.

Reference Type
Journal Article | Research Support, N.I.H., Extramural
Authors
Blackwell JS Jr, Wilkinson ST, Mosammaparast N, Pemberton LF
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