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Genomics > Epigenetics, TEs, Sex Chromosomes > Flashcards

Epigenetics, TEs, Sex Chromosomes Flashcards

1
Q

What is the function of DNA methylation?

A

prevent gene expression!

  • Hypermethylation in cis regulatory regions can prevent gene expression
  • DNA methylation is a way to control retrotransposons
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2
Q

How is DNA methylation detected?

A

You can detect DNA methylation using southern blots with methylation sensitive and insensitive enzymes

You can detect DNA methylation by bisulfite sequencing: conversion of unmethylated cytosines to uracils with bisulfite & then sequencing

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3
Q

What are the patterns of DNA methylation?

A

Methylation patterns vary during development and in different cell types

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4
Q

Where does DNA cytosine methylation typically occur?

A

Typically occurs in a CG dinucleotide context

also can occur in CHG or CHH (H=A, T, or C)

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5
Q

Functions of histone methylation and acetylation

A

Cause changes in chromatin structure

- Affect gene expression either positively or negatively

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6
Q

What are the patterns of histone methylation and acetylation?

A

Patterns vary during development and in different cell types

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7
Q

Where does histone methylation typically occur?

A

H3 & amp; H4 – H3K4me2

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8
Q

Where does Histone acetylation and deacetylation typically occur?

A

Typically occur on lysines (K) on tails of H3 & H4

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9
Q

What is the mechanism of histone acetylation?

A

Histone acetyltransferases adds acetyl groups on lysines (K) on tails of H3 & H4

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10
Q

What is the mechanism of histone deacetylation?

A

Histone deacetylases (HDAC) removes acetyl groups on lysines (K) on tails of H3 & H4

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11
Q

Histone methylation is often part of ________ chromatin and ________ gene expression

A

Histone methylation is often part of condensed chromatin and helps prevent gene expression

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12
Q

How to go from euchromatin to heterochromatin?

A

Histone methylation
Histone deacetylation
Corepressor complexes

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13
Q

How to go from heterochromatin to euchromatin?

A

Histone acetylation

Coactivator complexes

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14
Q

What is the effect of histone acetylation?

A

DNA unravels from heterochromatin –> euchromatin as histone modifications are added

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15
Q

What is the effect of histone deacetylation?

A

DNA condenses from euchromatin –> heterochromatin

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16
Q

How do DNA methylation and histone modifications interact?

A

Methyl C binding protein MECP2 binds methylated DNA & recruits histone deacetylases

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17
Q

What are histone modifications?

A

A combination of different molecules can attach to the ‘tails’ of proteins called histones. This alters the activity of the DNA around them.
i.e. Acetylation and deacetylation

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18
Q

How can histone acetylation be altered and studied?

A

Acetylation can be altered with trichostatin A: it induces acetylation & allows you to study effects of acetylation

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19
Q

What is the mechanism of DNA cytosine methylation

A

Methyl group is added to fifth of cytosine by DNA methyltransferase

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20
Q

What are the two main components of the epigenetic code?

A

DNA methylation and Histone modifications

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21
Q

What is DNA methylation?

A

Methyl marks added to certain bases that repress gene activity

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22
Q

What are the mechanisms of transcriptional silencing?

A

1) Methylation of promoter regions

2) Chromatin remodeling: euchromatin to heterochromatin

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23
Q

Human X size

A

Medium sized chromosome, about 1000 genes

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24
Q

Human X gene traits

A
  • Genes biased towards those involved in sex-specific characteristics & reproduction, as well as in brain function
  • Gene set mostly conserved in placental mammals.
25
Q

Human X and Y interactions

A

Most of the X & Y do not recombine, except for pseudoautosomal region

26
Q

Human Y size

A

Small chromosome, ~45 genes plus a few pseudogenes

- mostly satellite repeats

27
Q

Human Y gene traits

A
  • SRY gene: testis determining factor
  • Most genes have homologs on X
  • Genes mostly involved in sex determination and spermatogenesis
28
Q

Differentiation of the X & Y from an ancient autosome

A 
Autosome
- acquired sex determining locus
Proto-X,Y (Y has TDF)
- accumulate male advantage genes
X specific (MSY - Male specific region)
- recombination suppressed
PAR
- Y mutation and deletion
X and Y
29
Q

Mammalian X and Y evolution

A

Thought to have evolved from autosomes

  1. One of ancestral chromosomes acquired a sex determining gene SRY
  2. Recombination was GRADUALLY suppressed
  3. Massive gene deletion and pseudogene formation on the Y
30
Q

Xist and X chromosome inactivation

A

Xist RNA spreads out to chromosome arms

Xist RNA coats chromosome

31
Q

Ancient and added regions on the human X and Y

A

PAR – pseudoautosomal region
YAR – added region
YCR – ancient conserved region

32
Q

Mammalian Y chromosome degradation

A
  • Few genes remain on Y; chromosome shrunk
  • Forces thought to cause degradation:
  • Higher mutation on Y than on X: point mutations, indels
  • Less selection on non-recombining chrosmosome
33
Q

Which of the following is NOT true about the human Y chromosome?
A) It contains ancient and added regions
B) There are many satellite repeat regions
C) Most genes do not have homologs on the X
D) It has a pseudoautosomal region at the tip

A

C) Most genes do not have homologs on the X

34
Q

X chromosome inactivation – imprinting

A

Occurs by heterochromatin formation:

  • Silenced X is highly methylated and deacetylated
  • Initiated at X inactivation centre and spreads along the X chromosome
35
Q

What does Xist stand for?

A

Xist – X inactive specific transcript

Long non-coding RNA – 17Kb

36
Q

Xist vs TsiX

A

Both are long non-coding RNA

  • Xist is expressed only on inactive X chromosome
  • TsiX is expressed on active X
37
Q

What is TsiX?

A

TsiX – long non-coding RNA

  • antisense to Xist
  • expressed on active X
38
Q

How does Xist function?

A
  • Accumulates along X chromosome to be inactivated & facilitates heterochromatin formation;
  • helps recruit other factors involved
  • Starts at X activation centre & spreads outwards
39
Q

What is the function of Tsix?

A

binds to Xist & represses it

40
Q

What is the ZW system?

A

Sex chromosome systems in some vertebrate groups

41
Q

How to determine sex in ZW system

A

ZW – female, ZZ – male

kinda the reverse

42
Q

Who has ZW system?

A

ZZ/ZW: snakes, birds turtles,

ZZ/ZW multi: lizards, amphibians,
fish - (XY or ZW, temperature dependent)

43
Q

XY vs ZW

A

Y and W – highly heterochromatic and few genes, smaller

- Mammalian XY and bird ZW have different sets of genes and no sequence homology

44
Q

Autonomous TEs

A

contains protein(s) involved in transposition

45
Q

Non-Autonomous TEs

A

Does not contain protein(s) involved in transposition

- must get them from a closely related auto. TE

46
Q 
Which of the following types of TEs do not have terminal repeats?
A) DNA transposons
B) LTR retrotransposons
C) Non-LTR retrotransposons
D) All of them have terminal repeats
A

C) Non-LTR retrotransposons

47
Q

LTR retrotransposons — long terminal repeats

A

2 coding regions:

Reverse transcriptase, protease, RNAase, integrase

48
Q

DNA transposons — class 2

A

TE excise & insert elsewhere in genome: cut & paste Transposase recognizes terminal repeats

49
Q

Non-LTR retrotransposons — no terminal repeats

A

Contains Endonuclease, reverse transcriptase
- no terminal repeats
LINEs – long interspersed nuclear elements
SINEs – short interspersed nuclear elements

50
Q

RNA Elements - Class 1

A

mRNA transposition intermediate Often present in high copy numbers

51
Q

Transposon dynamics and effects on genome structure:

A

• Nested retrotransposons: Nested TEs that inserted into other TEs
- Can lead to greatly increased distance between genes and increased genome size

52
Q

TE Transposition Mechanisms

A
  1. Transposition (cut and paste)
  2. Replicative retrotransposition
  3. Target site primed reverse transcription
53
Q

Non-LTR RetroTransposition Mechanism

A

Target site primed reverse transcription

54
Q

Target site primed reverse transcription mechanism

A

Transcription
Priming and reverse transcription
Second strand synthesis
Completion of integration

55
Q

LTR Retrotransposon mechanism

A

Replicative retrotransposition

56
Q

Replicative retrotransposition mechanism

A 
“Copy paste”
Transcription
Reverse transcription
Transport of cDNA to nucleus
Integrase enzymes integrate into target
57
Q

DNA Transposons mechanism

A

Transposition (cut and paste)

58
Q

Transposition (cut and paste) mechanism

A

“Cut and paste”
Transposase binding
Transposase Excision
Integration to target

Genomics (9 decks)

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