Epigenetics Flashcards
What are epigenetics?
Epigenetics = changes in organisms caused by modification of gene expression rather than alteration of the genetic code
What is a genome? What is an epigenome?
Genome
The complete set of genes/genetic material present in a cell or organism
About 3 billion base pairs in humans
Epigenome
Epi (Greek for over or above)
What bits of the genome are actually used
Gene silencing versus gene expression
What is the difference between genetic and epigenetic factors?
Genetic is static
Epigenome is flexible
Changes with age and interactions with environment
Begins before conception and continues throughout your life
Can be subtle, cumulative effects that make them difficult to predict what the final outcome will be
What is an example of how epigenetics can be different in identical twins?
Olivia Murphy developed acute lymphoblastic leukaemia when two years old, but her twin sister Isabella is “healthy”
Identical twins develop from the same genome and within the same amniotic membrane
Allows some exchange of cells between Olivia and Isabella
Including “pre-leukaemic” cells in Olivia that are also present in Isabella
But only in Olivia have they progressed to leukaemia
Acute lymphoblastic leukaemia often develops spontaneously from fusion of two genes
Differences between twins (due to epigenetics) increase throughout their lives as genes are switched on and off
What are multigenerational and transgenerational epigenetics?
In females because germ cells are produced in developing fetus
Effect F1 and F2 directly and F3 indirectly
Effects observed in F1 and F2 generation result of direct exposure = multigenerational
Effects observed in F3 generation that had no direct exposure = transgenerational
In males, germ cells are not produced in developing fetus
Effect in F1 generation is direct – multigenerational
Effect in F2 generation result of indirect exposure = transgenerational
What can be delayed due to epigenetics?
You can delay aging or disease by following a healthy diet and lifestyle, etc. due to epigenetics
What is the Barker hypothesis?
Thrifty phenotype
Low availability of nutrients during prenatal stage followed by improvement in nutritional availability in childhood causes increased risk of metabolic disorders
Diabetes type II, obesity, coronary heart disease
What are the four mechanisms of epigenetic gene regulation?
DNA methylation - cytosines
Micro and small RNAs
Histone modification - histones
Chromatin architecture
What is involved in DNA structure and packing?
Double helix
Packing 2nm
1st level around histones = nucleosome
Beads on s string connected by linker DNA
Histone string is wrapped into a tight helical fibre
This further coils into a thick supercoil
Approx 300nm
Further looping and folding compacts DNA further
DNA packing tends to prevent gene expression by preventing transcription proteins from accessing DNA
What is the architecture of chromatin?
Changes shape of histone/DNA complex
ATP dependent remodelling complexes regulate gene expression
Alter the contact between DNA and histones
Alter the path of the DNA as it winds around the histones
What is involved in histone modification?
Post-translational modification of histone proteins
- Acetylation (A)
- Methylation (M)
- Phosphorylation (P)
- Ubiquitylation (U)
Most of these modifications are on lysine (K) Active genes - H3K4me3 - H3K36me3 Repressed genes - H3K27me3 - H3K9me2/3
Histone acetylase (HAT) Associated with “open” accessible DNA
Histone deacetylase (HDAC) Associated with “closed” inaccessible DNA
What is the function of HDAC inhibitors?
HDAC inhibitors are being used to increase gene transcription for genetic conditions:
Opening up DNA
They could also modify epigenetic changes
What is DNA methylation and what does it do?
Methyl groups can be added or removed from cytosine
DNA methylation usually represses gene transcription
Gene silencing
Methylation patterns are tissue specific and heritable
Methylation interferes with binding transcriptional activators
