TY - JOUR
T1 - Mice develop normally without the H10 linker histone
AU - Sirotkin, Allen M.
AU - Edelmann, Winfried
AU - Cheng, Genhong
AU - Klein-Szanto, Andres
AU - Kucherlapati, Raju
AU - Skoultchi, Arthur I.
PY - 1995/7/3
Y1 - 1995/7/3
N2 - 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 Hit, and the replacement linker histone H10. H10 accumulates in terminally differentiating cells from many lineages, at about the time when the cells cease dividing. To investigate the role of H10 in development, we have disrupted the single-copy H10 gene by homologous recombination in mouse embryonic stem cells. Mice homozygous for the mutation and completely lacking H10 mRNA and protein grew and reproduced normally and exhibited no anatomic or histologic abnormalities. Examination of tissues in which H10 is normally present at high levels also failed to reveal any abnormality in cell division patterns. Chromatin from H10-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 H10 by occupying sites that normally contain H10. Our results indicate that despite the unique properties and expression pattern of H10, its function is dispensable for normal mouse development.
AB - 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 Hit, and the replacement linker histone H10. H10 accumulates in terminally differentiating cells from many lineages, at about the time when the cells cease dividing. To investigate the role of H10 in development, we have disrupted the single-copy H10 gene by homologous recombination in mouse embryonic stem cells. Mice homozygous for the mutation and completely lacking H10 mRNA and protein grew and reproduced normally and exhibited no anatomic or histologic abnormalities. Examination of tissues in which H10 is normally present at high levels also failed to reveal any abnormality in cell division patterns. Chromatin from H10-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 H10 by occupying sites that normally contain H10. Our results indicate that despite the unique properties and expression pattern of H10, its function is dispensable for normal mouse development.
KW - Chromatin
KW - Gene inactivation
KW - Gene targeting
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U2 - 10.1073/pnas.92.14.6434
DO - 10.1073/pnas.92.14.6434
M3 - Article
C2 - 7604008
AN - SCOPUS:0029059469
SN - 0027-8424
VL - 92
SP - 6434
EP - 6438
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 14
ER -