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.

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16 thoughts on “DNA and chromatin regulation | Biomolecules | MCAT | Khan Academy”

  1. This was great! Just thought I'd point out though that CpG islands refer to the fact that Cytosine is linked via a phosphodiester bond with Guanine along the same strand of DNA. It's not referring to the fact that Cytosine forms hydrogen bonds with Guanine across complementary strands (although this does happen). Other than that, keep up the good work 🙂 These videos help me tons for my uni exams

  2. DNA methylation is a process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription.

  3. CpG islands are long repeats of CG twomers. The fact that C pairs with G is irrelevant and the 'p' in 'CpG' stands for phosphodiester.

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