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increasing again by day 28 (Hyldig et al. 2011b). Another study investigating
imprinted gene methylation reprogramming in pig PGCs showed that this process is
asynchronous and takes place over several days (Hyldig et al. 2011a). For instance,
IGF2R (Insulin Growth Factor Receptor 2) is demethylated in early gonadal PGCs
(by day 22), whereas the IGF2-H19 cluster is demethylated later at around day 25
(Hyldig et al. 2011a). In the case of the imprinted gene PEG10, complete demeth-
ylation was determined by day 27 (Wen et al. 2010 ). Furthermore, the methylation
status of repetitive sequences was also shown to be erased in PGCs between days 28
and 31 (Petkov et al. 2009 ; Hyldig et al. 2011a), suggesting that at this stage pig
PGCs have the lowest levels of methylation. Similar asynchrony in imprinted gene
demethylation has been shown in the human germ line (Gkountela et al. 2013 ).
Concomitant with changes in DNA methylation, reduction in histone H3K9me2
was shown in mouse PGCs from around E7.5 to E8.75, followed by an increase in
H3K27me3 from E9.25 until E13.5 (Seki et al. 2005 ). These changes occur during a
very narrow window of time in mice. H3K9me2 and H3K27me3 reprogramming
have also been described in pig PGCs; however, these changes are detected over a
protracted period between days 15 and 21, consistent with the longer developmental
period of pigs (Hyldig et al. 2011a). By E13.5 mouse PGCs have high levels of
repressive chromatin marks H3K9me3 and H3K27me3, whereas the permissive
marks H3K9ac and H2A.Z are very low (Seki et al. 2005 ). This is in contrast to find-
ings in human gonadal germ cells that show high levels of the active chromatin marks
H3K9ac and H2A.Z and low levels of repressive chromatin marks (Gkountela et al.
2013 ; Almstrup et al. 2010 ). In contrast, HP1 (Heterochromatin Protein 1) levels are
low in gonadal PGCs of both species (Seki et al. 2005 ; Bartkova et al. 2011 ). The
differences in histone profiles need to be studied in other animal models to determine
whether they may reflect differences in reproductive features between species.
8.6.5 Conclusions
The brief overview presented here highlights the great progress made over the past
century and how the new knowledge has contributed to a better understanding of
how germ cells form. Importantly, a better knowledge of the developmental charac-
teristics of the germ line of other mammals may enable us to model human disease
in relevant species.
Acknowledgments The authors would like to thank Dr. Malgorzata Kloc (Houston Methodist
Hospital and THMRI) and Kenneth Dunner Jr. (High Resolution Electron Microscopy Facility at
MD Anderson Cancer Center, Houston) for their generosity in providing the electron micrographs
shown in Fig. 8.5a–d. We are also very appreciative of the in situ hybridizations provided by Dawn
Owens shown in Fig. 8.5e–j. We would also like to thank Anita Cheung who compiled the data
shown in Table 8.2. Delany Rodriguez did an outstanding job of creating Figs. 8.8 and 8.9 and in
helping to edit the text. The authors would like to acknowledge support from NIH to M.L.K.
(R21HD072340; R01GM102397) and CCSG grant NIH P30CA016672 to K.D.
T. Aguero et al.