Epigenetic gene regulation Flashcards
Theories as to why genomic imprinting exists?
Genetic conflict, Dosage compensation, placental development, prevention of parthenogenesis
What is genetic conflict?
Maternal and paternal genome seem to compete for maternal resources
What is parthenogenesis?
Asexual reproduction where a female can produce a fertilised egg
What are generally the function of imprinted genes?
Foetal growth regulation, metabolism regulation and behavioural regulation
What is maternal foetal interaction?
Imprinted genes in the baby produce products that alter maternal resource allocation
Examples of outcomes of maternal foetal interaction?
Altered transport capacity of placenta
How does a foetus signal to the mother?
Producing fetal/placental hormones that modify the mothers metabolism
Effect on mothers of a mutation in Peg3 gene?
Poor mother–> it is the “maternal care gene” mothers wont make nests, are indifferent to offspring. It also affects milk release in mice
What is BAT?
Brown adipose tissue
What is the haig hypothesis?
Mothers know that the offspring that they are carrying is theirs, but fathers arent sure if the offspring is theirs-> paternal genes are there to compete against other paternal genes to ensure that their foetus grows faster and outcompetes other potential offspring–> promotes taking of maternal resources. Mother thinks ab future pregnancies and so doesn’t want to use all materna resources
Issue with haig parental conflict hypothesis?
Little proof
Coadaptation theory of imprinting?
Imprinted genes act co-adaptively to optimize foetal development as well as optimising maternal provisioning and nurturing.–> paternally expressed genes are expressed in both the placenta and the hypothalamus
Role of paternally expressed genes in haig parental conflict hypothesis?
Growth promoting
Role of maternally expressed genes in haig parental conflict hypothesis?
Growth inhibiting
Lighter coloured square in a TAG meaning?
Lower frequency of interaction between those two regions
Overall, what does H19 regulate?
Growth restriction
Three overall classes of things that are needed for epigenetic mechanisms to work properly?
Writers, readers, erasers
What is an epigenetic writer?
Enzyme that establishes the epigenetic mark
What is an epigenetic reader?
The molecules that respond to the epigenetic marks
What is an epigenetic eraser?
Things that can remove epigenetic marks
What are writers for DNA methylation?
DMNTs and TET enzymes
What are writers for histone acetylation?
HATs (histone acetyl transferases)
What are the erasers for histone deacetylation?
HDACs (histone deacetylases)
Effect of acetylating histones?
Opens chromatin conformation, more easy for DNA to be bound to
Effect of deacetylasing histones?
More closed chromatin conformation–> DNA is harder to access
How does noncoding RNA help with histone acetylation?
Acts as a scaffold
Where do HDACs and HATs bind?
Histones
What are HDACs and HATs recruited by?
TFs, noncoding RNAs
What are readers of histone acetylation called?
Bromodomain proteins (BRD)
What do BRDs promote the assembly of?
Transcriptional complexes
What can BRDS recruit?
Components involved in growth (+ve or -ve)
What is the usual effect of DNA methylation on TFs?
DNA methylation usually repels TFs
What are methyl binding proteins (MBD proteins)?
Proteins that can bind to methylated DNA and act as a suppressive protein
Effect of MBDs?
They can prevent the TF from binding instead of the methylation
How do MBDs prevent TFs from binding?
MBD can occupy the promoter region
What kind of protein is MeCP2?
MBD
What can MeCP2 do other than bind methylated DNA?
Recruits silencing factors (e.g. histone deacetylases, chromatin remodelers), act as a splicing regulatory regions
Effect of MeCP2 binding to methylated exon?
Exon is included in the mature mRNA when it otherwise wouldn’t have been
Which chromosome is the MeCP2 gene on?
X
What disease does MeCP2 gene mutations cause?
Rett Syndrome
Why is epigenetic a good target for medicines?
Dont need to go into the genome, just tweak how it is being used
