8 - epigenetics Flashcards

(74 cards)

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
5hmC stands for
5-hydroxymethylcytosine
26
where is 5hmC found
embryonic stem cells | brain
27
role of 5hmC
promotes gene expression during active demethylation
28
what role does DNA methylation play in genetic development and functioning
- 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
29
what is chromatin
found in the nucleus | combination of DNA as well as histone proteins
30
why are histone proteins important
they package DNA into chromatin | regulate DNA accessibility
31
two varieties of chromatin
euchromatin | heterochromatin
32
features of euchromatin
less compact | active
33
features of heterochromatin
compact | generally not active
34
nucleosome
basic unit of DNA condensation --> form the repeating units DNA wound around 8 histone proteins
35
features of nucleosomes
highly conserved largest protein component of chromatin repeating unit joined to other nucleosomes by linker DNA
36
what makes up each histone octamer
2 copies of the histones H2A, H2B, H3 and H4
37
features of histone modifications
dynamic | highly regulated
38
epigenetic writer
lays down histone modifications
39
epigenetic eraser
removes histone modifications
40
role of epigenetic regulators
possess specialised domains that allow proteins to 'read' the chromatin modifications and bind to them at specific regions and facilitate gene transcription
41
what does TAD stand for
topologically associated domains
42
what is a TAD
a sequence of DNA that interacts with itself part of the 3D genome
43
histone core
octamer of 4 histone proteins
44
types of histone modification
``` phosphorylation acetylation methylation ubiquitylation biotinylation ```
45
histone acetylation
catalysed by HAT enzymes reduces +ve charge to relax chromatin increases access of transcription factors to DNA
46
effect of histone acetylation on nucleosome binding
reduces affinity of the histone tail for adjacent nucleosomes
47
HAT
histone acetyltransferase
48
HDAC
histone deacetylase
49
bromodomain
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
histone tails
form H bonds with adjacent nucleosomes | sites for covalent modification
51
H3K27ac
a modification to DNA packaging protein Histone H3 associated with higher activation of transcription factors therefore an important enhancer mark of acetylation
52
H3K4
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
H3K9ac
marker of activation of transcription factors
54
ncRNA
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
two groups of ncRNA involved in epigenetic processes
``` short ncRNA (<200 nts) long ncRNA (>200 nts) ```
56
function of micro RNAs
short ncRNA repress gene expression assemble into RNA-induced silencing complex
57
properties of microRNA
tissue-specific highly regulated involved in development, differentiation, proliferation and apoptosis
58
biogenesis of microRNA
pri-miRNA --> pre-miRNA --> mature miRNA
59
mechanism of action of miRNA
hybridizes to target mRNA and inhibit translation
60
epigenetics in development
epigenetic profile is erased and reset during gametogenesis
61
epigenetic imprints
genes that have been altered epigenetically and have evaded the reprogramming of the epigenome
62
paternal imprinting
when the allele from father is switched off due DNA methylation so the allele is only inherited from the mother
63
parental conflict hypothesis
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
describe male genome in terms of parental conflict hypothesis
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
X chromosome inactivation
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
environmental influences on the epigenetic profile
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
when is epigenome highly sensitive to environment | and why
embryogenesis and perinatal period - DNA synthesis rate is high - elaborateDNA methylation patterns for normal tissue development are established
68
agouti mouse example
genetically identical mouse look very different differences due to DNA methylation changes manipulated by mothers diet (zinc, methionine, choline, folate, B12)
69
importance of dutch hunger winter 1944-45
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
factors that affect the epigenome
``` diet drug abuse toxins/pollutants radiation psychosocial factors medication climate hormones random differences ```
71
transgenerational epigenetic inheritance
caused by environmental exposure in 1st generation passed onto subsequent generations some epigenetic marks must be resistant to epigenome erasing
72
how can environmental impacts affect 2 generations
e.g. mother smoking while baby inside her which also has reproductive cells
73
what is epigenetics - SIMPLE
reversible regulation of gene expression
74
examples of metal exposure that may alter epigenome
arsenic lead mercury