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Tessarz and Kouzarides 2014 ). Importantly, functionality of key histone
modifications is more conserved across eukaryotic kingdoms than DNA methyla-
tion (for further reading, see Allis et al. 2007 ). Importantly, not every histone
modification is a true epigenetic mark, i.e., exists as a stable mark maintained
through S-phase and cell division. Some of the marks are simply deposited as a
consequence of some event (e.g., transcriptional activation, DNA damage) but are
not specifically maintained. Next, we will provide a brief overview of chromatin
remodeling during mammalian OET (reviewed in detail in Kimmins and Sassone-
Corsi 2005 ; Burton and Torres-Padilla 2010 , 2014 ; Gill et al. 2012 ; Rivera and
Ross 2013 ) with a specific focus on clearance of parental histone marks, which
can be seen as a path toward erasure of ancestral cellular identity and establish-
ment of pluripotency.
During germ cell development in the mouse, histone modifications undergo a
major “reset” upon entry of primordial germ cells into the genital ridge. Next,
differentiating male and female germ cells deposit various histone modifications
across their genomes. At the end of germ cell development and at the onset of
OET, parentally deposited histone modifications take dramatically different paths
in the two differentiating germ cells.
10.4.3 Protamine/Histone Exchange During Spermatogenesis
Parental histone modifications are essentially completely erased together with the
nucleosomal chromatin structure at the end of spermatogenesis during the so-called
protamine/histone exchange (reviewed in Kimmins and Sassone-Corsi 2005 ; Braun
2001 ). Protamines are proteins used for tight packaging of paternal genomes in
sperm heads. During the final stages of spermatogenesis, paternal chromatin under-
goes complex remodeling. Its final stage involves sperm-specific transition proteins,
which are subsequently replaced by protamines (Kimmins and Sassone-Corsi
2005 ). While the reason for protamine/histone exchange is unknown, it has clear
consequences for the histone code, which is almost completely erased.
However, detailed analysis of sperm chromatin revealed that 1–10 % of his-
tones are retained in the mouse and human spermatozoa, respectively (Brykczynska
et al. 2010 ). Furthermore, retained histones carried specific modifications, and
histone retention was not random but rather associated with a distinct promoter
set in human sperm (Brykczynska et al. 2010 ). In particular, H3K4me2 (active)
mark was found in promoters of genes involved in spermatogenesis and cellular
homeostasis, while H3K27me3 (repressive) mark was associated with develop-
mental promoters. It was proposed that residual histones contribute to the paternal
heterochromatin formation in human zygotes (van de Werken et al. 2014 ).
However, subsequent studies suggested that nucleosome retention is predomi-
nantly associated with gene deserts and not developmental promoters (summa-
rized in Saitou and Kurimoto 2014 ). Therefore, the exact contribution of
nucleosomal retention to the early embryo still needs to be elucidated.
P. Svoboda et al.