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epigenetic alterations we've spent a lot
of time thinking about epigenetics in
the genetics courses so epigenetics
again above the genome traditionally we
consider epigenetic factors to be
heritable changes that are not to the
DNA but to the way that DNA is packaged
and how it is accessed and we know that
these epigenetic factors now can change
throughout our lives and alter how and
when various genes are expressed in the
great variety of cells that we have so
these changes in chromatin state in
essence are regulating the expression of
genes and we've definitely spoken about
epigenetics being one of the factors
that regulates gene expression so when
we consider epigenetic factors I think
that you could probably write down at
least three different epigenetic
alterations that could happen so go
ahead and try that out and then let's
move forward and look a quick review of
what those are first of all we can have
histone modifications histones are the
cores around which DNA is wrapped and
depending on where those histones are
located DNA may be either accessible for
transcription or if it's wound tightly
around the histone inaccessible for gene
transcription these histone
modifications can include addition of
acetyl groups to the tails and changes
in the wrapping of the histone tails how
tightly they hold the DNA onto
themselves and again that lends itself
to accessibility issues on the DNA
another thing is in epigenetic
alterations we consider are how
methylation patterns happen you know
that areas that are highly condensed
heterochromatin and we have tight
packing and again lack of access to
genes by the transcriptional mechanisms
there's a connection of DNA methylation
patterns to the development and
progression of Alzheimer's disease and
how certain proteins fold in there
we will definitely cover Alzheimer's
disease in a future lecture in a lot
more detail but either way another
epigenetic alteration and all of these
epigenetic alterations lend themselves
to the concept of chromatin remodeling
so remodeling the areas that are
condensed versus opened and thus the
regions that are available for
transcription and translation
so in general we see decreasing levels
of heterochromatin associated with aging
and epigenetic remodeling or chromatin
remodeling actually is changed by some
environmental stimuli and this is one of
the very active fields of research at
the moment and how some of these
environmental modifications to the let's
say not DNA the epigenetic factors can
actually become heritable and we're
finding that they can so that's a really
exciting field at least to me at the
moment next let's consider loss of
Proteus stasis clearly if we have
changes in transcription rates and
frequencies of a variety of different
genes then we have a loss of Proteus
stasis simply meaning that cells perhaps
lose the ability to do quality control
on their own protein production and the
protein production has gone awry because
of these other modifications and insults
to the DNA a reactive oxygen species all
of these different things
we see that the loss of Proteus stasis
in beta amyloid plaques and tau proteins
and such that we see
and Alzheimer's and Parkinson's we also
see the disruption of protein
homeostasis in cataracts that's
responsible for the cloudiness that
occurs and cataracts so again disorders
clearly associated with loss of Proteus
stasis or homeostasis of the proteins
things are getting a little bit
dysregulated so accumulation of these
damaged proteins as we see in
Parkinson's and Alzheimer's disease
clearly cause some phenotypic effects
even can be toxic if not just
interrupting signaling
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