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Nat Struct Mol Biol. 2010 Nov;17(11):1343-51. doi: 10.1038/nsmb.1911. Epub 2010 Oct 17.

The program for processing newly synthesized histones H3.1 and H4.

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1
Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, New York, USA.

Abstract

The mechanism by which newly synthesized histones are imported into the nucleus and deposited onto replicating chromatin alongside segregating nucleosomal counterparts is poorly understood, yet this program is expected to bear on the putative epigenetic nature of histone post-translational modifications. To define the events by which naive pre-deposition histones are imported into the nucleus, we biochemically purified and characterized the full gamut of histone H3.1-containing complexes from human cytoplasmic fractions and identified their associated histone post-translational modifications. Through reconstitution assays, biophysical analyses and live cell manipulations, we describe in detail this series of events, namely the assembly of H3-H4 dimers, the acetylation of histones by the HAT1 holoenzyme and the transfer of histones between chaperones that culminates with their karyopherin-mediated nuclear import. We further demonstrate the high degree of conservation for this pathway between higher and lower eukaryotes.

PMID:
20953179
PMCID:
PMC2988979
DOI:
10.1038/nsmb.1911
[Indexed for MEDLINE]
Free PMC Article

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