Biology Reference
In-Depth Information
numerous neuropeptides and hormones. Such an inherent complexity indi-
rectly suggests the operation of multiple regulatory mechanisms, which
would be needed to enable the proper timing of puberty. Recent evidence
has suggested that such mechanisms likely include, in addition to the
classical
transcriptional regulation of sets of genes, nontranscriptional regulatory phe-
nomena, such as epigenetics and microRNAs (miRNAs). Admittedly, the
precise roles of such
nonclassical
mechanisms are yet to be fully exposed, as
recognition of their participation in the control of puberty
escaped
conven-
tional endocrine/molecular analyses until very recently.
In this context, evidence is mounting that the regulation of key compo-
nents of the central pathways governing puberty onset involve epigenetic
mechanisms. Epigenetics is defined as inheritable information that is not
encoded by the nucleotide sequence of a given gene, but rather by modifica-
tions of the DNA or the protein component of chromatin, histones (
Paulsen,
Tierling, & Walter, 2008; Sims, Magazinnik, Houston, Wu, & Rice, 2008;
Van Emburgh &Robertson, 2008
). Incorporation of methyl groups to CpG
islands in the DNA is the only known form of epigenetic modification of
DNA, which is a general mark of gene repression (
Paulsen et al., 2008;
Van Emburgh & Robertson, 2008
). In contrast, epigenetic changes on his-
tones may include a diversity of modifications, such acetylation, methylation,
and phosphorylation (
Sims et al., 2008
), whose net effect in terms of gene
repression or activation depends on the histone and residue subjected tomod-
ification (
Sims et al., 2008
). Of note, epigenetic changes may participate in
the control of long-term developmental modifications as well as in rapid
modulatory events; both phenomena are seemingly involved in the regula-
tion of key aspects of puberty (
Ojeda, Dubay, et al., 2010
). However, studies
addressing the potential participation of epigenetics in the control ofmamma-
lian puberty have not been undertaken until very recently.
In a series of elegant studies, Ojeda and colleagues have very recently
provided compelling evidence for the involvement of epigenetic regulatory
mechanisms in the central control of female puberty. Thus, profound chan-
ges in the patterns of DNA methylation have been found to take place in the
hypothalamus during puberty in female rodents (
Lomniczi et al., 2013
). In
addition, the hypothalamic expression of two key transcriptional repressors
of the Polycomb group (PcG), namely Eed and Cbx7, has been shown to
decrease during pubertal progression due to enhanced methylation of their
promoters (
Lomniczi et al., 2013
). Accordingly, systemic pharmacological
blockade of DNA methylation in juvenile female rats was found to delay
the timing of puberty (
Lomniczi et al., 2013
). Analogous results, albeit of
