Lecture 4 Genetics (vertical) Annika

Question 1

Inheritance of mutations:

1. What is the difference between somatic and germ lime mutations?

Answer 1

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Question 2

1. What is the definition of epigenetics/epigenomics?
2. What are the three things that chemical modifications are determined by?
3. Chemical modifications can be 2 things?
4. What is the difference between epigenetic and epigenomics?

Answer 2

Chemical covalent modifications of DNA i.e. of individual genes (epigenetic) or genome (epigenomics) that result in changes to the regulation of genes or genomes, without altering the DNA sequence.

Question 3

Everyone is biochemically unique

“Every individual has his/her own unique makeup of gene products, which are produced in response to the combined inputs of the genome sequence and one’s particular set of _______ _______ and _______ ______.”

“One’s different types of environmental exposures and lifestyle choices at different times during one’s life chemically modify DNA sequences (and proteins) which modify gene expression, thus create _____ ____.”

Answer 3

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Question 4

1. What is chromatin? Are there different forms of chromatin?
2. What are histones?
3. Loosely packed chromatin (beads on a string) form what nm fibre?
4. What about densely packed?
5. Is chromatin dynamic and moves bw the 10 and 30 or is it stable?

Answer 4

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Question 5

1. What does a nucleosome consist of? (core and DNA)
2. Histone proteins have a ____ charged tail of aa’
3. Because you have the +vely charged tails that bind to the -vely charged DNA, what happens to the chromatin?
4. How does that regulate gene expression?
5. So what are the two types of chromatin?

Answer 5

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Question 6

What are the two aspects of epigenetic/epigenomic gene expression thing aka what are the two ways to move between the 10nm and 30nm

Answer 6

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Question 7

Chemical modification of histone proteins:

1. Addition of various _____ _____ to certain aa’ can inhibit or activate gene expression?

Answer 7

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Question 8

How do you get from 30nm to 10nm?

1. By post translational covalent chemical modifications of certain aa’ in the histone tails - what two are we focusing on?
2. By histone variants that what?
3. What’re the two others?

Answer 8

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Question 9

Histone acetylation
-to what aa’ is it the addition of acetyl group?

1. Does it make gene inaccessible or accessible?
2. How does it work?

Answer 9

1. Well, since you’re going from 30nm to 10nm, it should make it accessible
2. Positively charged bc amino group bu the gets acelayted and then you dont carry the charge so acetlyation neutralises the +ve charge on lysine It’s the positive chargeos on tails that allows the DNA to attract etc so when you neutralise the +ve chargen then dont get same level of attraction. Dna wont be compacted and genes can transcribed bc transition from tight to loose euchromatin from heterochrimatin. But then if you remove acetly group then move from eu to hetero

Question 10

Histone demethylation:

1. The removal of methyl groups (CH3) from what two aa’?
2. How does that (usually) make genes accessible for transcription?

Answer 10

Because it’s the opposite of methylation. When you remove the hydrophobic methyl groups, you lessen the hydrophobic interactions between the histone tails so they won’t pack together and thus favour the euchromatin.

Question 11

Histone methylation on Lys and Arg

1. Does it have an effect on the charge?
2. Then how does it work?
3. Methylation of histones can either decrease transcription or increase (very uncommon) transcription of genes depending on what?
4. So in euchromatin - is it more acetylation or methylation?

Answer 11

Te hydrophobic methyl groups attract eachother condensing the DNA packing (even more than usual!)

Question 12

So histone modifications remodel the chromatin structure directly regulating gene activity by what?

How can histone modifications regulate gene activity indirectly?

Answer 12

Chemical modifications of histone protein can recruit other proteins to regulate gene expression where the other proteins activate or inactivate transcription by remodelling chromatin (e.g. physically removing histone or bringing more in)

Question 13

Histone variants can control the gene expression - how?

what are the non-canonical (non-recognised) variants of histone proteins:

• can have very ____ or less _____ functions (via remodelling the chromatin structure and/or recruiting other proteins
• often expressed when?
• act by replacing what at particular nucleosomes?

Answer 13

There are many different histone proteins and have properties that create localised hetero or euchromatin regions. This is bc they all have slightly different tails and e.g. if they have less Arg then less lysine etc then you get less acetylation then can control gene expression bc it’ll be densely packed

Question 14

DNA methylation

1. What base do you add the methyl group?
2. How does DNA methylation inhibit gene expression? (2)
3. What cytosines are methylated?

Answer 14

The methylation groups are recognised and bound by methyl-binding proteins. These MBPs will physically block transcription factors and RNA pol 2 accessing the promoter OR the same bound MBP recruits enzymes that deacetylates the histones at that particular region thereby remodelling the chromatin to heterosexual