Epigenetics of Reproduction in Animals - Building the Most Complex Structure on Earth - page 78

methylation/demethylation and histone acetylation/deacetylation that lead to chro-
matin remodeling) and AS. Epigenetic signatures such as differential methylation
and histone acetylation in the exon regions indicate that AS may be regulated epige-
netically ( Kornblihtt et al., 2009; Zhou et al., 2012 ).
Histone acetylation and deacetylation, along with histone methylation, and his-
tone modifications generally, are involved in the assembly and dynamic rearrange-
ments of the spliceosome ( Gunderson et al., 2011 ). Modifications to the histone
structure facilitate the binding of chromatin-binding proteins and serve to recruit
splice factors. The deacetylation in the gene body not only prevents internal initia-
tion of transcription but also restricts spliceosome assembly to the exons alone.
Histone acetylation alterates the transcription rate and, just like histone methyla-
tion, it is believed to influence AS by recruiting spliceosomal subunits. For exam-
ple, one of the subunits of the spliceosome, U2snRNP, is recruited by the HAT Gcn5
( Hnilicová and Staněk, 2011 ), and polypyrimidine tract binding protein, which
is associated with chromatin, by binding pre-mRNA, modulates the AS of several
genes ( Hnilicová and Staněk, 2011; Sharma et al., 2008 ). Histone H3K9me3 (H3 tri-
methyl Lys9) is a regulator of AS ( Hnilicová and Staněk, 2011 ), whereas HDACs
influence selection of splice sites ( Hnilicová et al., 2011 ).
Recent evidence shows that, along with AS, especially during the development,
alternative transcripts are generated by a novel mechanism, the “alternative transcrip-
tion,” which precedes AS and consists of the production of different pre-mRNAs by
changing the start and/or end of transcription ( Pal et al., 2011 ).
The experimental evidence of the role of histone modification and chromatin
remodeling in the context of the evidence on the neural origin of information for
changes epigenetic structures (histone modification/chromatin remodeling) presented
earlier in this chapter, suggest that the nervous system may play a crucial role in AS
of pre-mRNAs in metazoans.
At present, we are far from a real understanding of the control system in unicel-
lulars and plants; hence, the ultimate source of information for the regulation of AS
in these groups is still a mystery.
Epigenetic Information and Signal Cascades
We obviously oversimplify when we speak of interactions between genes and the
external environment. The relationship is neither direct nor linear; more often than
not, both lack physical contact to interact. In between are a number of separat-
ing biological macro- and microstructures. A plant or an animal organism is under
the constant action of various environmental variables, but genes, within the cell
nucleus, are well protected against their action. Even if genes were to come in con-
tact with external agents, they would not respond adaptively by switching off or on,
if they could respond at all. Notwithstanding, genes respond adaptively to external
or internal stimuli, such as changes in the temperature of the environment, humidity,
length of the day, day-night and seasonal cycles, changes in the social environment,
presence of predators, or changes in the level of hormones and other chemicals in
body fluids.