Stage-dependent redistributions of acetylated histones in nuclei of the early preimplantation mouse embryo.
In the preimplantation mouse embryo, activation of the embryonic genome is accompanied by a transient enrichment of histone H4 acetylated at lysines 5, 8, and 12 at the nuclear periphery (Worrad et al., 1995: Development 121:2949-2959). In the present report, we use laser-scanning confocal microscopy and a new panel of antibodies to define the distribution of specific acetylated isoforms of the other three core histones in mouse embryos at the 1- to 4-cell stage. We find that histone H3 acetylated at lysine 9 and/or 18 (H3.Ac9/18) and the single acetylated form of H2A (H2A.Ac5) become transiently enriched at the nuclear periphery in the 2-cell embryo. In contrast, H3.Ac14, H3.Ac23, and acetylated H2B, like H4.Ac16, remain distributed throughout the nucleoplasm. The staining intensity with antisera to H3.Ac9/18, even at the periphery was weak compared to that obtained with antisera to acetylated H4. A brief period of culture, however, in the presence of the inhibitor of histone deacetylases trichostatin A (TSA) or trapoxin increased labeling. Thus, the steady-state level of H3.Ac9/18 at the nuclear periphery and H3.Ac14 and H3.Ac23 in the nuclear interior is relatively low, but turnover remains high. The localization of selected acetylated isoforms of H3 and H2A at the nuclear periphery was independent of ongoing transcription or of cytokinesis, but did require DNA replication. We propose a model in which the selective, replication-dependent acetylation and deacetylation of zygotic chromatin at the nuclear periphery mediates the programming of zygotic transcription.
Stein
P
P
Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, USA.
Worrad
D M
DM
Belyaev
N D
ND
Turner
B M
BM
Schultz
R M
RM
D000107:Acetylation; D000546:Amanitins / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016590:Aphidicolin / Q000494:pharmacology; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D018507:Gene Expression Regulation, Developmental; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000276:immunology / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D007106:Immune Sera; D051379:Mice; D018613:Microscopy, Confocal; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010455:Peptides; D013194:Staining and Labeling; D014158:Transcription, Genetic / Q000187:drug effects
D000546:Amanitins; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D007106:Immune Sera; D019384:Nucleic Acid Synthesis Inhibitors; D010455:Peptides; C067070:trapoxin A; D016590:Aphidicolin; C012589:trichostatin A