Biology Reference
In-Depth Information
males and females regarding the hormonal, temporal, structural, and func-
tional control of germ-cell development, which shape gametic epigenomes
in a highly sexually dimorphic manner. The various chromatin components
and the histone and DNA modifications that define the sperm and oocyte
genomes have just started to be characterized on the genome-wide level.
2.1. Sex-specific chromatin organization and histone
modifications
Enzymes involved in histone modification and chromatin organization are
strictly required for proper gametogenesis (
Gill et al., 2012
). Changes in
chromatin modifications and expression of specific histone modifiers are
among the first markers of emerging germ-cell precursors, amid surrounding
somatic cells of the early embryo (
Kota & Feil, 2010
). At this early stage,
global histone modification patterns are indistinguishable in male and female
germ cells. At the end of gametogenesis, however, mature oocyte and sperm
chromatin profiles are dramatically different, reflecting the specific con-
straints exerted on the two parental germlines during their differentiation.
To reach the oocyte, the sperm must travel along both the male and
female reproductive tracts. To enhance motility and protection from
DNA damage, the sperm nucleus adopts an extreme state of condensation,
made possible via the replacement of canonical histone proteins by smaller
basic structural proteins, termed protamines. This transformation in DNA
packaging occurs in a sequential manner, starting in transcriptionally inactive
spermatids with the incorporation of testis-specific histone variants,
followed by a phase of histone hyperacetylation which may provide an
accessible environment for the final histone eviction and substitution with
protamines (
Gaucher et al., 2010
). It was believed that in this way the sperm
could contribute little to no histone-based information to the progeny.
However, biochemical and microscopy methods suggest that 10-15% of
the paternal genome can persist in the form of histone-containing nucleo-
somes in human sperm (
Brykczynska et al., 2010; Gusse &Chevaillier, 1980;
Tanphaichitr, Sobhon, Taluppeth, & Chalermisarachai, 1978
), a feature
confirmed by the detection of several H3 histone variants by immunofluo-
rescence (
van der Heijden et al., 2008
). Recent genome-wide mapping of
nucleosome distribution indicated that retention occurs nonrandomly, with
a twofold enrichment at regulatory sequences around transcription start sites,
and a significant overrepresentation at the promoters of transcription factors
and signaling molecules that guide embryonic development (
Brykczynska
et al., 2010; Hammoud et al., 2009
). Loci enriched in histones are not
