epigenetics Flashcards
epigenetics definition
the study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself.
transcription factors
- proteins that bind to the section of DNA that comes just before the gene and regulate transcription rate
- activators stimulate the rate of transcription, helps RNA polymerase bind to the start of the target gene
- repressors decrease the rate of transcription
how much of the genome is non-coding?
98%
roles of epigenetic marks
- mark the beginnings and ends of genes
- alter how we read each gene by silencing/activating them
epigenome
all the epigenetic modifications of the DNA genome and its associated histone proteins
chromatin
DNA is wrapped around histone proteins making up chromatin
packing of chromatin
- tightly packed chromatin (heterochromatin): DNA is less accessible to the transcriptional machinery (transcription can occur less easily)
- loosely packed chromatin (euchromatin): DNA is more accessible to the transcriptional machinery (transcription can occur more easily)
chromatin structure
- DNA wraps 1.75 times around a histone octamer (8 units of histones)
- attraction between +ve histone and -ve DNA
DNA methylation
- addition of a methyl group (CH3) to DNA
- usually happens at CpG sites (where C is next to G on the DNA strand)
- silences genes
How does DNA methylation silence genes?
methylated CpGs are associated with condensation of the chromatin because methylated CpG is bound by methylated CpG binding proteins: MeCP1 & MeCP2 which can alter transcription
How can DNA methylation be copied mitotically?
DNMT (DNA methyltransferases) enzymes recognise hemi-methylated daughter strand and lay down methylation on the daughter strand when DNA is replicated.
X inactivation
- an epigenetic dosage compensation mechanism in mammals so that males and females have the same dose of genes on the X chromosome
- one X chromosome in females is silenced so both males and females have 1 X chromosome
- the cell makes a choice individually as to which X chromosome to inactivate (maternal or paternal) and this choice is mitotically heritable to all daughter cells
- the inactivated X chromosome shrivels up into a Barr body
- X inactivation happens in females
Kleinfelter’s Syndrome
- when males have XXY instead of the normal XY
- X inactivation has to occur in males with this syndrome
histone acetylation
- acetylation involves adding acetyl groups to lysine amino acids, neutralising their +ve charge and therefore reducing the attraction between the histones and DNA -> increased accessibility -> increased transcription
- histones are acetylated by histone acetyltransferases (HAT)
- acetyl groups are removed by histone deacetylases (HDAC)
SAHA
SAHA works by inhibiting HDACs from acting on tumour suppressor genes -> increased expression of normal tumour suppressor genes which can fight the uncontrollable division of cells causing the cancer
5-azacytidine
5-azacytidine works by inhibiting DNMT from acting on tumour suppressor genes, so there is less methylation laid down, increased gene expression of tumour suppressor genes to fight cancer cells
Yamanaka factors
four specific genes which can rewind any adult cell to a stem cell
Hayflick Limit
-defines the no. of possible cell divisions (40-60) and depends on the length of telomeres, which decrease in standard cells with every cell division
Waddington’s Epigenetic Landscape
- ball at top of hill = zygotes, undifferentiated, all genes switched on
- ball at bottom of hill = fully differentiated
- just as a ball is difficult to roll up a hill, so is reprogramming a differentiated cell to become undifferentiated
- reprogramming occurs during fertilisation to allow 2 fully differentiated gametes to produce a zygote
Dutch Hunger Winter
- food supplies cut off in Netherlands WWII so people of all social classes received 400-800cals per day
- maternal malnutrition had most significant effect on baby’s health in later life when exposed to poor nutrition at the beginning of pregnancy
- this is because epigenetic enzymes would have laid down marks while trying to compensate for poor nutrition
- the cells have been epigenetically adjusted to make the most of available food so when adequate food is later presented -> obesity and related conditions
Thrifty Phenotype Hypothesis
In 1992, C.N.Hales & D.J.Barker proposed that environmental factors in utero, particularly undernutrition, may influence the risk of metabolic syndrome of the individual later in life
- the validity of the findings is now generally accepted
- could be because if the foetus is exposed to malnutrition in utero, it will be prepared for survival in an environment in which resources are likely to be short. Yet, if they go on to lead an affluent life, their thrifty phenotype could lead to overeating and subsequently obesity.
tumour suppressor genes
- tell the cell to stop dividing (red light)
- if hyper-methylated -> can lead to cancer
- examples: BRCA 1/2, p53
proto-oncogenes
- tell the cell to divide (green light)
- an oncogene is any gene that causes cancer
- proto-oncogenes can turn into oncogenes when a mutation permanently activates the gene
- if hypo-methylated -> can lead to cancer
examples: HER2
epigenetic reprogramming
-erasure of epigenetic marks during fertilisation so that the differentiated gametes can fuse to become the undifferentiated zygote
