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TMS exam > 8 - epigenetics > Flashcards

8 - epigenetics Flashcards

1
Q

definition of epigenetics

A

the reversible regulation of gene expression
mediated principally through changes in DNA methylation and chromatin structure
occurring independently of the DNA sequence

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2
Q

why is DNA sequence regulation important

A

determines what specific mRNA molecules are synthesised

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3
Q

what does epigenetic regulation determine

A

how much mRNA is made
where mRNA in synthesised
when mRNA is synthesised

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4
Q

two main types of epigenetic alterations

A

dna methylation

histone modification

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5
Q

dna methylation SIMPLE

A

chemical modification of the DNA

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6
Q

histone modification SIMPLE

A

chemical modification of the proteins that surround the DNA

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7
Q

how do epigenetics act like molecular switches

A

they have the ability to “shut down” or “rev up” expression of genes

e.g. if lots of histones are acetylated, the transcription factors can bind to genes and the gene is turned on

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8
Q

what did tissue and cell type profiling find

A

that different cell types are characterised by different genomes

relationships are often mirrored between similar cell/tissue types in different people

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9
Q

method of dna methylation

A

displacement of transcription factors ad attraction of methyl-binding proteins

addition of a methyl group to the C-5 position of cytosine residues

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10
Q

is dna methylation uniform across the genetic code

A

no

genome consists of unmethylated segments interspersed with methylated regions

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11
Q

where is 5-methylcytosine concentrated

A

at CpG islands

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12
Q

CpG islands

A

hot spot of CG
(where CG concentration is greater than 50%)

often in promoter regions

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13
Q

result of methylating CpG islands

A

dysregulates gene transcription

inhibits transcription factors from binding directly and indrectly

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14
Q

indirect transcription factor binding

A

via altered histone acetylation

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15
Q

DNMTs

A

group of enzymes that function during different times in the cell cycle
DNA methyl transferases

catalyse transfer of methyl group from SAM to convert it to SAH

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16
Q

what does SAM stand for

A

S-adenosyl methionine

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17
Q

SAH

A

S-adenosyl homocysteine

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18
Q

DNMT1

A

maintenance methylase

maintains pattern of DNA methylation after DNA replication

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19
Q

DNMT subtypes

A

DNMT1
DNMT2
DNMT3a and 3b

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20
Q

role of DNMT3a and DNMT3b

A

de novo methylases

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21
Q

demethylation

A

removal of a methyl group from nucleotides in DNA

can be passive or active

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22
Q

result of DNA demethylation of a gene promoter

A

transcriptional activation and gene expression

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23
Q

passive demethylation

A

takes place in the absence of methylation of newly synthesised DNA strands by DNMT1 during several replication rounds

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24
Q

Active DNA demethylation

A

mediated by multiple enzymes and can occur independent of DNA replication.

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25
Q

5hmC stands for

A

5-hydroxymethylcytosine

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26
Q

where is 5hmC found

A

embryonic stem cells

brain

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27
Q

role of 5hmC

A

promotes gene expression during active demethylation

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28
Q

what role does DNA methylation play in genetic development and functioning

A
  • long term silencing of genes
  • silencing of repetitive elements e.g. transposons
  • X-chromosome inactivation
  • establishment and maintenance of imprinted genes
  • suppression of expression of viral genes
  • carcinogenesis
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29
Q

what is chromatin

A

found in the nucleus

combination of DNA as well as histone proteins

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30
Q

why are histone proteins important

A

they package DNA into chromatin

regulate DNA accessibility

31
Q

two varieties of chromatin

A

euchromatin

heterochromatin

32
Q

features of euchromatin

A

less compact

active

33
Q

features of heterochromatin

A

compact

generally not active

34
Q

nucleosome

A

basic unit of DNA condensation –> form the repeating units

DNA wound around 8 histone proteins

35
Q

features of nucleosomes

A

highly conserved
largest protein component of chromatin
repeating unit

joined to other nucleosomes by linker DNA

36
Q

what makes up each histone octamer

A

2 copies of the histones H2A, H2B, H3 and H4

37
Q

features of histone modifications

A

dynamic

highly regulated

38
Q

epigenetic writer

A

lays down histone modifications

39
Q

epigenetic eraser

A

removes histone modifications

40
Q

role of epigenetic regulators

A

possess specialised domains that allow proteins to ‘read’ the chromatin modifications and bind to them at specific regions and facilitate gene transcription

41
Q

what does TAD stand for

A

topologically associated domains

42
Q

what is a TAD

A

a sequence of DNA that interacts with itself

part of the 3D genome

43
Q

histone core

A

octamer of 4 histone proteins

44
Q

types of histone modification

A 
phosphorylation 
acetylation 
methylation
ubiquitylation
biotinylation
45
Q

histone acetylation

A

catalysed by HAT enzymes
reduces +ve charge to relax chromatin
increases access of transcription factors to DNA

46
Q

effect of histone acetylation on nucleosome binding

A

reduces affinity of the histone tail for adjacent nucleosomes

47
Q

HAT

A

histone acetyltransferase

48
Q

HDAC

A

histone deacetylase

49
Q

bromodomain

A

protein domain that recognizes acetylated lysine residues, such as those on the N-terminal tails of histones.

e.g. preferentially recognises acetylated histone tails

50
Q

histone tails

A

form H bonds with adjacent nucleosomes

sites for covalent modification

51
Q

H3K27ac

A

a modification to DNA packaging protein Histone H3

associated with higher activation of transcription factors therefore an important enhancer mark of acetylation

52
Q

H3K4

A

epigenetic chemical modification involved in the regulation of gene expression
–> addition of 3 methyl groups

associated with the activation of transcription of nearby genes

53
Q

H3K9ac

A

marker of activation of transcription factors

54
Q

ncRNA

A

non-coding RNA

does not code for proteins
functions to regulate gene expression at the transcriptional and post-transcriptional level

makes up 97% of the genome

55
Q

two groups of ncRNA involved in epigenetic processes

A 
short ncRNA (<200 nts)
long ncRNA (>200 nts)
56
Q

function of micro RNAs

A

short ncRNA

repress gene expression
assemble into RNA-induced silencing complex

57
Q

properties of microRNA

A

tissue-specific
highly regulated
involved in development, differentiation, proliferation and apoptosis

58
Q

biogenesis of microRNA

A

pri-miRNA –> pre-miRNA –> mature miRNA

59
Q

mechanism of action of miRNA

A

hybridizes to target mRNA and inhibit translation

60
Q

epigenetics in development

A

epigenetic profile is erased and reset during gametogenesis

61
Q

epigenetic imprints

A

genes that have been altered epigenetically and have evaded the reprogramming of the epigenome

62
Q

paternal imprinting

A

when the allele from father is switched off due DNA methylation so the allele is only inherited from the mother

63
Q

parental conflict hypothesis

A

hypothesis for the evolution of genomic imprinting

states that the inequality between parental genomes due to imprinting is a result of the differing interests of each parent in terms of the evolutionary fitness of their genes

64
Q

describe male genome in terms of parental conflict hypothesis

A

genes that encode for imprinting gain greater fitness through the success of the offspring at the expense of the mother

paternally expressed genes tend to be growth-promoting

65
Q

X chromosome inactivation

A

paternal X chromosome (Xp) is selectively inactivated in all cells in early mammal embryos

Xp is reactivated in blastocyst stage

Xp or Xm is then randomly inactivated permanently

66
Q

environmental influences on the epigenetic profile

A

epigenetic marks are highly sensitive to environment

dynamic nature allows organism to respond to environment without changing DNA sequence

genome can acquire/lose a methyl group easily

67
Q

when is epigenome highly sensitive to environment

and why

A

embryogenesis and perinatal period

  • DNA synthesis rate is high
  • elaborateDNA methylation patterns for normal tissue development are established
68
Q

agouti mouse example

A

genetically identical mouse look very different
differences due to DNA methylation
changes manipulated by mothers diet (zinc, methionine, choline, folate, B12)

69
Q

importance of dutch hunger winter 1944-45

A

individuals in the womb at the time of the famine received less nutrients therefore less methylation of the imprinted IGF2 gene compared to unexposed siblings

70
Q

factors that affect the epigenome

A 
diet
drug abuse
toxins/pollutants
radiation 
psychosocial factors
medication
climate
hormones
random differences
71
Q

transgenerational epigenetic inheritance

A

caused by environmental exposure in 1st generation
passed onto subsequent generations
some epigenetic marks must be resistant to epigenome erasing

72
Q

how can environmental impacts affect 2 generations

A

e.g. mother smoking while baby inside her which also has reproductive cells

73
Q

what is epigenetics - SIMPLE

A

reversible regulation of gene expression

74
Q

examples of metal exposure that may alter epigenome

A

arsenic
lead
mercury

TMS exam (22 decks)

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