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

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.

Pubmed ID: 20953179

Authors

  • Campos EI
  • Fillingham J
  • Li G
  • Zheng H
  • Voigt P
  • Kuo WH
  • Seepany H
  • Gao Z
  • Day LA
  • Greenblatt JF
  • Reinberg D

Journal

Nature structural & molecular biology

Publication Data

November 22, 2010

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM064844
  • Agency: NIGMS NIH HHS, Id: R01 GM064844
  • Agency: NIGMS NIH HHS, Id: R01 GM064844-08
  • Agency: NIGMS NIH HHS, Id: R37 GM037120
  • Agency: NIGMS NIH HHS, Id: R37 GM037120-26
  • Agency: NIGMS NIH HHS, Id: R37GM037120
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Acetylation
  • Active Transport, Cell Nucleus
  • Autoantigens
  • Cell Cycle Proteins
  • Cell Line
  • Cytoplasm
  • Dimerization
  • Epigenesis, Genetic
  • Histone Acetyltransferases
  • Histone Chaperones
  • Histones
  • Humans
  • Karyopherins
  • Models, Genetic
  • Nuclear Proteins
  • Protein Processing, Post-Translational
  • RNA Interference
  • Saccharomyces cerevisiae