Genomic imprinting Flashcards
(30 cards)
Examples of:
Writers/Initiators
Maintainers
Readers
Erasers
Dnmt3
lncRNa
Histone methyltransferases
Dnmt1
DNA methylation binding proteins
TFs
Deacetylases
Demethylases
Epigenome functions
Maintains DNA integrity in cell cycle
Regulates gene expression
Responds to internal + external enviros
Epigenetic therapy
e.g. in cancer
- targets
- effects
DNMT inhibitors
HDAC inhibitors
TSG expression
Apoptosis
Immunomodulation
Nucelar transfer
- Gynogenetic
- Androgenetic
Replace male pronucleus w/ female one
= (2 female nuclei)
Replace female pronucleus w/ male one
What happens in an oocyte doesn’t exclude the 2nd polar body?
Activates 2nd polar body
= Parthenogenetic
Why do we need 2 parental genomes for normal development?
2 female pronuclei
= hardly any extra embryonic tissue
- tiny embryo that doesn’t develop
(no placental support)
2 male pronuclei
= lots of ExEmbryonic tissue
- hardly any embryo
Prader-Willi syndrome
Uniparental disomy of 15q11-q13
Deletion of paternal copy
Angelman syndrome
Uniparental disomy of 15q11-q13
Deletion of maternal copy
Genomic imprinting
- define
Subset of genes epigenetically silenced on 1 parental allele during germ-line development
Genomic imprinting
- is it maintained?
Silencing maintained throughout development
Reset in germ-line of next gen.
= a transgenerational epigenetic phenomenon
Theories for why genomic imprinting occurs
> genetic conflict
- competition of genomes for maternal resources
> dosage compensation
> placental development
> prevention of parthenogenesis
Haig parental conflict hypothesis
AKA Kinship theory
Mothers know offspring is their’s
Males need to compete w/ other to get genes into next gen.
Mother doesn’t invest all resources into 1st pregnancy
- going to have more
Males don’t know if a child is theirs so need to compete for resources
- want their offspring to outcompete other genomes
Haig parental conflict
- female vs. male characteristics
Female:
Growth suppressing
Preservation of maternal resources
TSGS
Male:
Growth promoting
Competition of His offspring for maternal resources
Oncogenes
Selfish gene concept
= purpose of life is to get YOUR genome into the next gen.
Imprinted genes
- monogamous species
Fewer imprinted genes as less reason to compete
However never always some cheating as never 100% monogamous
What happens when you cross a monogamous x polyandrous species ?
= imprinting defects
Coadaptation theory
Imprinted genes act co-adaptively to optimise foetal development
+ maternal provisioning + nurturing
Maternal provisioning
Size + energy content of eggs
Coadaptation
- e.g. Peg3
Subset of mainly paternally expressed genes expressed in placenta + hypothalamus of brain
If no Peg3
- > mother has no maternal instinct
- > leaves offspring
Imprinted genes
- genome organisation
MEGs + PEGs clustered
- assume they work together in a network
Primary hallmarks of imprinting
- DNA methylation
Methylated = inactive
- TFs can’t bind to closed chromatin
Demethylated
= active
DMR
AKA imprinting control regions
Differentially methylated regions
- different methylation status across samples
Primordial germ cells
- DNA methylation
Methylation imprints erased + re-established
Genital marks added when cells are at genital ridge
Embryonic reprogramming
- occurs in 2 major development phases
- in PGCs
- global demethylation
- > then remethylation
- > in fertilisation active demethylation of male pronucleus, slow demethylation of female pronucleus - Imprinted genes resistant after fertilisation
Promoter methylation model
Methylated promoter
= silenced allele
Unmethylated
= active allele
