Loss of heterochromatin protein 1 gamma reduces the number of primordial germ cells via impaired cell cycle progression in mice
- PMID: 21778144
- DOI: 10.1095/biolreprod.111.091512
Loss of heterochromatin protein 1 gamma reduces the number of primordial germ cells via impaired cell cycle progression in mice
Abstract
Signals from extraembryonic tissues in mice determine which proximal epiblast cells become primordial germ cells (PGCs). After their specification, approximately 40 PGCs appear at the base of the allantoic bud and migrate to the genital ridges, where they expand to about 25 000 cells by Embryonic Day (E)13.5. The heterochromatin protein 1 (HP1) family members HP1alpha, HP1beta, and HP1gamma (CBX5, CBX1, and CBX3, respectively) are thought to induce heterochromatin structure and to regulate gene expression by binding methylated histone H3 lysine 9. We found a dramatic loss of germ cells before meiosis in HP1gamma mutant (HP1gamma(-/-)) mice that we generated previously. The reduction in PGCs in HP1gamma(-/-) embryos was detectable from the early bud stage (E7.25), and the number of HP1gamma(-/-) PGCs was gradually reduced thereafter. Bromodeoxyuridine incorporation into PGCs was significantly reduced in E7.25 and E12.5 HP1gamma(-/-) embryos. Furthermore, a lower proportion of HP1gamma(-/-) PGCs than wild-type PGCs was in S phase, and a higher proportion, respectively, was in G1 phase at E12.5. Moreover, the proportion of p21 (Cip, official symbol CDKN1A)-positive HP1gamma(-/-) PGCs was increased, suggesting that the G1/S phase transition was inhibited. However, no differences were detected between fate determination, migration, apoptosis, or histone modification of PGCs of control embryos and those of HP1gamma(-/-) embryos. Therefore, the reduction in PGCs in HP1gamma(-/-) embryos could be caused by impaired cell cycle in PGCs. These results suggest that HP1gamma plays an important role in keeping enough germ cells by regulating the PGC cell cycle.
Similar articles
-
Primordial germ cells: what does it take to be alive?Mol Reprod Dev. 2004 May;68(1):1-4. doi: 10.1002/mrd.20056. Mol Reprod Dev. 2004. PMID: 15039942 Review.
-
BMP signaling regulates PGC numbers and motility in organ culture.Mech Dev. 2007 Jan;124(1):68-77. doi: 10.1016/j.mod.2006.09.005. Epub 2006 Sep 30. Mech Dev. 2007. PMID: 17112707
-
Heterogeneity of mouse primordial germ cells reflecting the distinct status of their differentiation, proliferation and apoptosis can be classified by the expression of cell surface proteins integrin α6 and c-Kit.Dev Growth Differ. 2009 Aug;51(6):567-83. doi: 10.1111/j.1440-169X.2009.01119.x. Epub 2009 Jul 6. Dev Growth Differ. 2009. PMID: 21314674
-
Lineage-specific expression of heterochromatin protein 1gamma in post-compaction, in vitro-produced bovine embryos.Reprod Fertil Dev. 2010;22(6):1022-31. doi: 10.1071/RD09265. Reprod Fertil Dev. 2010. PMID: 20591336
-
Mechanisms of germ-cell specification in mouse embryos.Bioessays. 2005 Feb;27(2):136-43. doi: 10.1002/bies.20178. Bioessays. 2005. PMID: 15666347 Review.
Cited by
-
Transcriptional quiescence in primordial germ cells.Crit Rev Biochem Mol Biol. 2018 Dec;53(6):579-595. doi: 10.1080/10409238.2018.1506733. Epub 2018 Oct 3. Crit Rev Biochem Mol Biol. 2018. PMID: 30280955 Free PMC article. Review.
-
On the relations of phase separation and Hi-C maps to epigenetics.R Soc Open Sci. 2020 Feb 26;7(2):191976. doi: 10.1098/rsos.191976. eCollection 2020 Feb. R Soc Open Sci. 2020. PMID: 32257349 Free PMC article.
-
Epigenetics of eu- and heterochromatin in inverted and conventional nuclei from mouse retina.Chromosome Res. 2013 Aug;21(5):535-54. doi: 10.1007/s10577-013-9375-7. Epub 2013 Aug 31. Chromosome Res. 2013. PMID: 23996328
-
Deletion of HP1γ in cardiac myocytes affects H4K20me3 levels but does not impact cardiac growth.Epigenetics Chromatin. 2018 Apr 17;11(1):18. doi: 10.1186/s13072-018-0187-z. Epigenetics Chromatin. 2018. PMID: 29665845 Free PMC article.
-
Down-regulation of HDAC5 inhibits growth of human hepatocellular carcinoma by induction of apoptosis and cell cycle arrest.Tumour Biol. 2014 Nov;35(11):11523-32. doi: 10.1007/s13277-014-2358-2. Epub 2014 Aug 17. Tumour Biol. 2014. PMID: 25129440
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials
Miscellaneous