Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/97198
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Type: | Journal article |
Title: | Contribution of the two genes encoding histone variant H3.3 to viability and fertility in mice |
Author: | Tang, M. Jacobs, S. Mattiske, D. Soh, Y. Graham, A. Tran, A. Lim, S. Hudson, D. Kalitsis, P. O Bryan, M. Wong, L. Mann, J. |
Citation: | PLoS Genetics, 2015; 11(2):e1004964-1-e1004964-23 |
Publisher: | Public Library of Science |
Issue Date: | 2015 |
ISSN: | 1553-7390 1553-7404 |
Editor: | Tremethick, D. |
Statement of Responsibility: | Michelle C. W. Tang, Shelley A. Jacobs, Deidre M. Mattiske, Yu May Soh, Alison N. Graham, An Tran, Shu Ly Lim, Damien F. Hudson, Paul Kalitsis, Moira K. O, Bryan, Lee H. Wong, Jeffrey R. Mann |
Abstract: | Histones package DNA and regulate epigenetic states. For the latter, probably the most important histone is H3. Mammals have three near-identical H3 isoforms: canonical H3.1 and H3.2, and the replication-independent variant H3.3. This variant can accumulate in slowly dividing somatic cells, replacing canonical H3. Some replication-independent histones, through their ability to incorporate outside S-phase, are functionally important in the very slowly dividing mammalian germ line. Much remains to be learned of H3.3 functions in germ cell development. Histone H3.3 presents a unique genetic paradigm in that two conventional intron-containing genes encode the identical protein. Here, we present a comprehensive analysis of the developmental effects of null mutations in each of these genes. H3f3a mutants were viable to adulthood. Females were fertile, while males were subfertile with dysmorphic spermatozoa. H3f3b mutants were growth-deficient, dying at birth. H3f3b heterozygotes were also growth-deficient, with males being sterile because of arrest of round spermatids. This sterility was not accompanied by abnormalities in sex chromosome inactivation in meiosis I. Conditional ablation of H3f3b at the beginning of folliculogenesis resulted in zygote cleavage failure, establishing H3f3b as a maternal-effect gene, and revealing a requirement for H3.3 in the first mitosis. Simultaneous ablation of H3f3a and H3f3b in folliculogenesis resulted in early primary oocyte death, demonstrating a crucial role for H3.3 in oogenesis. These findings reveal a heavy reliance on H3.3 for growth, gametogenesis, and fertilization, identifying developmental processes that are particularly susceptible to H3.3 deficiency. They also reveal partial redundancy in function of H3f3a and H3f3b, with the latter gene being generally the most important. |
Keywords: | Oocytes Zygote Spermatozoa Spermatocytes Chromatin Fetus Animals Mice Histones Meiosis Oogenesis Cell Survival DNA Replication Fertility Female Male |
Rights: | © 2015 Tang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
DOI: | 10.1371/journal.pgen.1004964 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1002316 http://purl.org/au-research/grants/nhmrc/545805 http://purl.org/au-research/grants/nhmrc/1031866 |
Published version: | http://dx.doi.org/10.1371/journal.pgen.1004964 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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hdl_97198.pdf | Published version | 20.85 MB | Adobe PDF | View/Open |
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