So, the regulation of
gene expression can be

modulated at virtually any
step in the process, from

the initiation of
transcription all the way to

post-translational
modification of a protein,

and every step in between.

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

that helps the cell to have

the versatility and the adaptability of

an efficient ninja, so
that it expends energy to

express the appropriate
proteins only when needed.

Or, you can think of the cell as

a lazy couch potato that wants to expend

the least amount of energy as possible.

So, starting at the
beginning of gene expression,

let's talk about gene regulation

as it pertains to DNA
and chromatin regulation.

Let's talk about the structure of DNA.

DNA is packed into
chromosomes in the form of

chromatin, also know as supercoiled DNA.

And so, chromatin is made up of DNA,

histone proteins, and
non-histone proteins.

And there are repeating
units in chromatin,

called nucleosomes, which are made up of

146 base pairs of double
helical DNA that is

wrapped around a core of eight histones.

And there are four different
types of histones within

this structure of eight
that you should be aware of.

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

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

Now, acetylation occurs at
the amino terminal tails

of these histone proteins
by an enzyme called

histone acetyltransferase,

which I'll just abbreviate as HAT.

And this is a reversible
modification, so the

acetylation of histones
is sort of kept in balance

by another enzyme that
removes these acetyl groups,

which is called histone
deacetylase, or HDAC.

The acetylation of histones leads to

uncoiling of this chromatin
structure, and this

allows it be accessed by
transcriptional machinery

for the expression of genes.

On the flip side of this,
histone deacetylation leads to

a condensed, or closed
structure of the chromatin,

and less transcription of those genes.

When these modifications that regulate

gene expression are inheritable,

they are referred to as
epigenetic regulation.

So, when it comes to
gene expression and DNA,

you can basically think of DNA

as coming in two flavors,

densely packed, and
transcriptionally inactive DNA,

which is called heterochromatin,
and then less dense,

transcriptionally active
DNA, which is euchromatin.

And I like to think of
heterochromatin as being

densely packed and hibernating,
like heterochromatin

and hibernating both begin
with H, kind of like a

bunch of densely packed bears that are

closed off in their cave for the winter,

whereas euchromatin is waiting there

with open arms, welcoming the

transcriptional machinery
to transcribe away.

Now often you will see
that histone deacetylation

is combined with another type of

DNA regulatory mechanism,

and that is DNA methylation, and

this occurs in a process
called gene silencing.

And this is a more
permanent method of sort of

down-regulating the
transcription of genes.

And DNA methylation
involves the addition of a

methyl group, which is a
carbon with three hydrogens,

to the cytosine, DNA nucleotides,

by an enzyme appropriately
called methyltransferase.

And this typically occurs in

cytosine-rich sequences
called CpG islands.

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

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

DNA methylation stably alters

the expression of genes, and so

it occurs as cells
divide and differentiate

from embryonic stem cells
into specific tissues.

And so this is essential
for normal development,

and is associated with
other processes, such as

genomic imprinting, and
x-chromosome inactivation,

topics for another discussion.

And abnormal DNA methylation has been

implicated in carcinogenesis, or the

development of cancer,
so you can see how the

normal functioning of DNA methylation is

a critical regulatory
mechanism for our cells.

Now, DNA methylation may effect

the transcription of genes in two ways.

First, the methylation of DNA itself

may physically impede the binding

of transcriptional proteins to the gene.

And second, and likely more important,

methylated DNA may be
bound by proteins known as

methyl cpg-binding domain proteins,

or MBDs, for short.

Now MBD proteins can then
recruit additional proteins

to the locus, or particular
location in a chromosome,

certain genes, such as
histone deacetylases,

and other chromatin
remodeling proteins, and this

modifies the histones, forming condensed,

inactive heterochromatin that is

basically transcriptionally silent.