BIOL 104 Lecture Notes - Lecture 4: Murray Barr, Barr Body, Down Syndrome

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13 May 2018
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Epigenetics:
So far, we have been discussing the flow of genetic information from DNA to RNA to Protein and how
mutations in the gene or promoter sequence can affect the function or the levels of the final protein.
This can lead to health issues because a protein should function in a specific cell type and at a specific
time.
However, these gene expression changes do not have to occur as a result of DNA mutation. Epigenetics
refers to genetic modifications that lead to physical variation without altering the nucleotide sequence.
As you know, a complex of transcription factors, along with RNA Polymerase, bind to
enhancers/silencers and the promoter to turn genes on or off. Recall the demonstration of a string
(DNA) wrapping around a finger (histones) that we had in lecture.
The positive charge of histones and the negative charge of the DNA allow both molecules to interact
really well. If the histone charge is “masked,” the DNA falls off the histone.
-The cell winds some regions of the genome tightly around histone proteins in order to shut a gene off.
If a region of the genome is tightly wound up, the transcriptional machinery cannot access the
promoter.
-The cell loosens DNA/histone complexes in some regions of the genome in order to turn a gene on. In
this case, the transcriptional machinery can easily access the promoter.
**The key moment in the switch in masking/demasking the histone charges is the methylation of DNA.
-DNA that is highly methylated is usually off and doesn’t make protein. -DNA that is not methylated is
usually “on” and does make protein.
I highlighted the craziness of this process by describing an extreme example of this…
X-inactivation -Males have 1 X chromosome -Females have 2 X chromosomes -Therefore, females have
double the number of X chromosome genes than males do.
This would be a problem for females because they would make double the amount of X chromosome
proteins. You already know what happens when there are too many copies of genes/proteins in a cell
(Down Syndrome, but more on that later). To combat this problem, females completely inactivate one
of their two X chromosomes in every cell in their body. The chromosome is so highly methylated that it
is wrapped tightly around histones to form a tiny dot under a microscope. This is called a Barr Body
because it was discovered by a dude named Murray Barr.
Epigenetics can help us explain how people develop health issues as they grow/age. This is particularly
true for monozygotic twins who are genetically identical. Why would two genetically identical people
have different personalities or susceptibilities toward disease? The answer could be epigenetics! -
Comparing the DNA methylation patterns of 3-year-old identical twins shows similarities. -Comparing
the DNA methylation patterns of 50-year-old identical twins shows many differences.
Therefore, DNA methylation/DNA packaging/gene expression changes occur as we grow/age. The
environment is known to play a role in modifying these DNA methylation patterns. In lecture, we
discussed two examples of environmental input shown to have this effect.
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Document Summary

So far, we have been discussing the flow of genetic information from dna to rna to protein and how mutations in the gene or promoter sequence can affect the function or the levels of the final protein. This can lead to health issues because a protein should function in a specific cell type and at a specific time. However, these gene expression changes do not have to occur as a result of dna mutation. Epigenetics refers to genetic modifications that lead to physical variation without altering the nucleotide sequence. As you know, a complex of transcription factors, along with rna polymerase, bind to enhancers/silencers and the promoter to turn genes on or off. Recall the demonstration of a string (dna) wrapping around a finger (histones) that we had in lecture. The positive charge of histones and the negative charge of the dna allow both molecules to interact really well.

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