Biology Reference
In-Depth Information
Hypothalamus
Kiss-1 neuron
Kisspeptin
GnRH neuron
GnRH
Brain
Pituitary
Gonadotrope cell
Acetylation of
histone H3
Ovary
Granulosa cell
Estradiol
Figure 2.7 Neural control of the signal cascade that leads to acetylation of histone H3 and,
consequently, induction of FSH-responsive genes and the synthesis of E2 by granulosa cells
surrounding the oocyte. Note that the epigenetic information necessary for H3 acetylation
flows from hypothalamic neurons via the FSH-secreting pituitary cells to granulosa cells,
where it induces FSH-responsive genes.
the transcription of FSH responsive genes necessary for granulosa cell differentia-
tion ( Salvador et al., 2001 ). But the epigenetic information that flows down to the
granulose cell histone originates farther upstream at the hypothalamic neurons that,
by secreting GnRH, induce the pituitary to secrete FSH ( Figure 2.7 ).
In a number of cases, histone acetylation and chromatin remodeling are induced
directly by chemical signals released by nerve endings. This is the case with the reg-
ulation of expression of the synaptic nAChR (nicotinic acetylcholine receptor) genes
in the neuromuscular junction (NMJ) ( Figure 2.8 ). Axon terminals of the motor neu-
rons release agrin ( Herndon et al., 2011; Ravel-Chapuis et al., 2007 ) and neuregu-
lin ( Ravel-Chapuis et al., 2007 ), which activate the receptor muscle-specific kinase,
which in turn triggers signal transduction pathways that lead to the activation of
GA-binding protein (GABP). The latter recruits HAT p300, which induces histone
acetylation causing chromatin to “open” and enabling the expression of AChR mem-
brane receptor genes.
All the examples presented earlier in this chapter show that the epigenetic infor-
mation embodied in methylated DNA and in modified histones is provided to them
by external factors rather than being generated in these structures. It is transmitted
to them via neurohormonal signal cascades along the hypothalamic-pituitary-target
endocrine glands axes that ultimately start in the CNS and via intracellular signal
transduction pathways ( Cabej, 2005 ) or via chemical signals released by nerve end-
ings that also originate in the CNS. It seems that the ultimate upstream source of
information that flows through neurohormonal cascades is the CNS.
 
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