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So, the regulation of
gene expression can be

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modulated at virtually any
step in the process, from

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the initiation of
transcription all the way to

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post-translational
modification of a protein,

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and every step in between.

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And it's the ability to regulate
all these different steps

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that helps the cell to have

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the versatility and the adaptability of

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an efficient ninja, so
that it expends energy to

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express the appropriate
proteins only when needed.

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Or, you can think of the cell as

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a lazy couch potato that wants to expend

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the least amount of energy as possible.

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So, starting at the
beginning of gene expression,

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let's talk about gene regulation

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as it pertains to DNA
and chromatin regulation.

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Let's talk about the structure of DNA.

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DNA is packed into
chromosomes in the form of

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chromatin, also know as supercoiled DNA.

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And so, chromatin is made up of DNA,

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histone proteins, and
non-histone proteins.

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And there are repeating
units in chromatin,

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called nucleosomes, which are made up of

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146 base pairs of double
helical DNA that is

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wrapped around a core of eight histones.

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And there are four different
types of histones within

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this structure of eight
that you should be aware of.

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And they're named H2A, H2B, H3, and H4,

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that's just the nomenclature
they've been given.

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Now, acetylation occurs at
the amino terminal tails

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of these histone proteins
by an enzyme called

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histone acetyltransferase,

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which I'll just abbreviate as HAT.

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And this is a reversible
modification, so the

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acetylation of histones
is sort of kept in balance

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by another enzyme that
removes these acetyl groups,

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which is called histone
deacetylase, or HDAC.

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The acetylation of histones leads to

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uncoiling of this chromatin
structure, and this

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allows it be accessed by
transcriptional machinery

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for the expression of genes.

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On the flip side of this,
histone deacetylation leads to

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a condensed, or closed
structure of the chromatin,

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and less transcription of those genes.

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When these modifications that regulate

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gene expression are inheritable,

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they are referred to as
epigenetic regulation.

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So, when it comes to
gene expression and DNA,

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you can basically think of DNA

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as coming in two flavors,

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densely packed, and
transcriptionally inactive DNA,

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which is called heterochromatin,
and then less dense,

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transcriptionally active
DNA, which is euchromatin.

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And I like to think of
heterochromatin as being

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densely packed and hibernating,
like heterochromatin

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and hibernating both begin
with H, kind of like a

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bunch of densely packed bears that are

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closed off in their cave for the winter,

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whereas euchromatin is waiting there

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with open arms, welcoming the

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transcriptional machinery
to transcribe away.

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Now often you will see
that histone deacetylation

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is combined with another type of

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DNA regulatory mechanism,

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and that is DNA methylation, and

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this occurs in a process
called gene silencing.

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And this is a more
permanent method of sort of

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down-regulating the
transcription of genes.

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And DNA methylation
involves the addition of a

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methyl group, which is a
carbon with three hydrogens,

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to the cytosine, DNA nucleotides,

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by an enzyme appropriately
called methyltransferase.

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And this typically occurs in

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cytosine-rich sequences
called CpG islands.

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Don't forget that cytosine
pairs with g, guanine,

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so that's why they're cg
islands that you'll find.

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DNA methylation stably alters

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the expression of genes, and so

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it occurs as cells
divide and differentiate

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from embryonic stem cells
into specific tissues.

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And so this is essential
for normal development,

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and is associated with
other processes, such as

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genomic imprinting, and
x-chromosome inactivation,

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topics for another discussion.

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And abnormal DNA methylation has been

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implicated in carcinogenesis, or the

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development of cancer,
so you can see how the

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normal functioning of DNA methylation is

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a critical regulatory
mechanism for our cells.

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Now, DNA methylation may effect

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the transcription of genes in two ways.

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First, the methylation of DNA itself

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may physically impede the binding

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of transcriptional proteins to the gene.

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And second, and likely more important,

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methylated DNA may be
bound by proteins known as

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methyl cpg-binding domain proteins,

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or MBDs, for short.

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Now MBD proteins can then
recruit additional proteins

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to the locus, or particular
location in a chromosome,

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00:05:05,589 --> 00:05:08,689
certain genes, such as
histone deacetylases,

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and other chromatin
remodeling proteins, and this

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modifies the histones, forming condensed,

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inactive heterochromatin that is

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basically transcriptionally silent.