Epigenetic reprogramming Flashcards
When does epigenetic reprogramming (global DNA demethylation and remethylation) occur during development? (2)
- In the germline when making gametes
- In the pre-implantation embryo after fertilisation
What happens to imprinted genes in the gametes?
Imprinted genes in gametes always exhibit the methylation pattern of the sex of the individual i.e. paternal in sperm and maternal in egg to be passed onto the next generation, regardless of whether that individual inherited the genes maternally or paternally
What happens to imprinted genes during development? (2)
- Imprinted genes bypass epigenetic reprogramming in the early embryo and persist in somatic tissues on either paternal or maternal chromosomes throughout embryogenesis and into adult life
- Imprinted genes are erased in the primordial germ cells of the early embryo before sex determination and then a new imprint is created in gametes, according to the chromosomal sex of the embryo
What is purpose of genome-wide epigenetic reprogramming in gamete formation? (5)
- Resets imprinted genes for the sex of the embryo for passing onto the next generation
- Erases acquired somatic epigenetic memories e.g. environmental (i.e. acquired during embryonic development so far)
- Facilitates gametogenesis
- Maintain the silencing of transposable elements to maintain genome integrity
- Reduces the mutation rate in the germline (lower than somatic cells)
What is the purpose of genome-wide epigenetic reprogramming in the pre-implantation embryo? (2)
- Resets zygotic epigenetic genome for naive pluripotency
- Some evidence of maternal vs paternal genome wars
What are PGCs? (2)
- Primordial germ cells
- Embryonic precursors to sperm/egg cells are specified around day 17 of embryonic development and migrate to the developing gonads at week 5-6
When does epigenetic reprogramming of the gametes happen?
Week 5-6 of embryonic development when the PGCs migrate along the genital ridge
When does epigenetic reprogramming of the pre-implantation embryo happen?
In the zygote immediately after fertilisation when there are still 2 separate maternal and paternal pronuclei present
What happens to the germline cells after epigenome erasure? (2)
- Gonadal germ cells undergo meiosis and gametogenesis during foetal development (extent of which is dictated by if sperm or eggs being made)
- Genome is re-methylated to acquire appropriate epigenetic signatures for the identity of the germ cell for generation of a future zygote by fertilisation
What happens to the genome during PGC migration? (3)
- Epigenetic memories erased by global DNA demethylation, genomic imprint erasure, X chromosome REactivation, reorganisation of chromosomes for meiosis (same in XY and XX embryos)
- XY germ cells then enter mitotic arrest (start meiosis during puberty)
- XX germ cells then enter meiosis and arrest at prophase I
How does germline DNA remethylation differ between male and female gametes? (3)
- Migratory PGCs become demethylated in early development (active and passive mechanisms)
- Remethylation at imprinting control regions in a sex-specific manner begins in spermatogonial stem cells during foetal development in males
- Remethylation at imprinting control regions in a sex-specific manner begins after birth in growing oocytes
Which genes escape global DNA demethylation in PGCs? (2)
- 4% of genomic loci remain methylated which are mostly associated with retrotransposable elements
- Mechanism is unknown but assumed that it is due to incomplete repression of DNA methylation pathway
Is post-fertilisation demethylation in the early embryo active or passive? (3)
- Paternal genome is demethylated by an active mechanism
- Female genome is demethylated by a passive mechanism that requires DNA replication
- Inherited genomic imprints (methylated/unmethylated) persist in somatic tissues (not reset)
How are imprinted loci protected during epigenetic reprogramming in the early embryo?
Mechanism unknown but long non-coding RNAs are a candidate mechanism
Lecture 9 epigenetics L3 lecture
