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.
Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, New York, USA.
Eric I
EI
Campos
Jeffrey
J
Fillingham
Guohong
G
Li
Haiyan
H
Zheng
Philipp
P
Voigt
Wei-Hung W
WH
Kuo
Harshika
H
Seepany
Zhonghua
Z
Gao
Loren A
LA
Day
Jack F
JF
Greenblatt
Danny
D
Reinberg
D000107:Acetylation; D021581:Active Transport, Cell Nucleus / Q000502:physiology; D001324:Autoantigens / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D044127:Epigenesis, Genetic; D051548:Histone Acetyltransferases / Q000378:metabolism / Q000502:physiology; D056488:Histone Chaperones / Q000378:metabolism; D006657:Histones / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
C491640:ASF1B protein, human; D001324:Autoantigens; D018797:Cell Cycle Proteins; D056488:Histone Chaperones; D006657:Histones; D028884:Karyopherins; C489390:NASP protein, human; D009687:Nuclear Proteins; D051548:Histone Acetyltransferases; C110880:histone acetyltransferase type B complex