Mice develop normally without the H1(0) linker histone.
H1 histones bind to the linker DNA between nucleosome core particles and facilitate the folding of chromatin into a 30-nm fiber. Mice contain at least seven nonallelic subtypes of H1, including the somatic variants H1a through H1e, the testis-specific variant H1t, and the replacement linker histone H1(0). H1(0) accumulates in terminally differentiating cells from many lineages, at about the time when the cells cease dividing. To investigate the role of H1(0) in development, we have disrupted the single-copy H1(0) gene by homologous recombination in mouse embryonic stem cells. Mice homozygous for the mutation and completely lacking H1(0) mRNA and protein grew and reproduced normally and exhibited no anatomic or histologic abnormalities. Examination of tissues in which H1(0) is normally present at high levels also failed to reveal any abnormality in cell division patterns. Chromatin from H1(0)-deficient animals showed no significant change in the relative proportions of the other H1 subtypes or in the stoichiometry between linker histones and nucleosomes, suggesting that the other H1 histones can compensate for the deficiency in H1(0) by occupying sites that normally contain H1(0). Our results indicate that despite the unique properties and expression pattern of H1(0), its function is dispensable for normal mouse development.
Sirotkin
A M
AM
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Edelmann
W
W
Cheng
G
G
Klein-Szanto
A
A
Kucherlapati
R
R
Skoultchi
A I
AI
D000818:Animals; D001483:Base Sequence; D002678:Chimera; D002843:Chromatin / Q000378:metabolism; D017931:DNA Primers; D004622:Embryo, Mammalian; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006657:Histones / Q000172:deficiency* / Q000235:genetics*; D006720:Homozygote; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000254:growth & development*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D013234:Stem Cells / Q000378:metabolism; D013737:Testis / Q000378:metabolism
D002843:Chromatin; D017931:DNA Primers; D006657:Histones