DNA Modification in Mammalian Brain HTML version

DNA modification in Mammalian Brain
DNA methylation is one of the most important and essential molecule in the epigenetic mark in the mammalian
development, genomic imprinting, X-inactivation, chromosomal stability and suppressing parasitic DNA element.
DNA methylation in neurons has also been recommended to play an important role for mammalian neuronal
functions, and learning and memory.
Epigenetics is a quickly evolving branch of biology that studies how temporal and spatial cellular
diversity is achieved from invariable genomic sequences. It tells how a single genome with a defined
number of genes can have radically diverse gene expression patterns and allows building a whole
organism with different cell types. That every cellular lineage has a different genomic distribution of
epigenetic features, such as histone variants, histone modifications and DNA modifications, which
engenders distinct gene expression profiles. There are certain examples of DNA, researchers have been
successful in describing (i) the epigenetic landscape of embryonic stem cells (ESCs) or induced
pluripotent stem cells (iPSCs), as opposed to somatic cells, (ii) stages of epigenetic alterations during
differentiation processes from ESCs or iPSCs to various cellular lineages, and (iii) the epigenetic
landscape of cancer cells.
In fact, there are many different and various evidences supporting the importance of epigenetic regulation
in neurons, there is more or less information for the neuronal epigenome than for other well-studied cell
types, such as ESCs or cancel cells.
It is acknowledged and found that human brain consists of billions of neurons forming a complex network
with precise spatio-temporal functions. Each neuron in the human brain works as functional unit which
receives, integrates and transmits information. Neurons can very possibly alter the ir electrophysiological
properties and responsiveness towards particular stimuli. Such neuronal plasticity requires sustained
alteration of the local synaptic strength as well as sustained alteration of globa l gene expression in the
nucle i, for timescales of hours, days or even years after the initial stimulus was present.
If you have ever tried recalling past events, you have had found it in your memory. Human memory often
lasts for many decades, whereas most mRNAs have half lives of minutes to hours and most proteins,
inc luding synaptic structural prote ins, have half-lives of less than a few days. DNA methylation is a
serious candidate for mediating long-term plasticity and memory. DNA methylation is chemically stable
with a half-life of over a thousand years. Mammalian DNA methyltransferase (Dnmt) 1 is active on
hemimethylated cytosine–guanine dinucleotide (CpG) in double-strand DNA. This allows for the self-
perpetuating nature of DNA methylation. The possibility of DNA modification being a key mechanism
for neuronal plasticity has been considered since the late 1960s and the disruption of contextua l fear
conditioning following injection of a methylation inhibitorwas shown in the 1970s. There are many more
important discoveries in mamma lian brains have been made; First, oxidation products of 5-
methylcytosine (5-mC), such as 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC) and 5-
carboxylcytosine (5-caC).
DNA modifications in the mammalian genome
The mammalian genome 5-methylcytosine (5-mC) one of the earliest discovered. 5-mC mostly appears in
the CpG, context in the mamma lian genome. When 5-mC is deaminated, 5-mC becomes thymine, which
is one of the four bases of DNA.