期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 17, 期 11, 页码 1343-U201出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.1911
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资金
- Howard Hughes Medical Institute
- US National Institutes of Health [GM064844, R37GM037120]
- Natural Sciences and Engineering Research Council of Canada
- Canadian Cancer Society Research Institute
- Deutsche Akademie der Naturforscher Leopoldina [LPDS 2009-5]
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.
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