Donovan 2 Flashcards
When is maternal RNA used during preimplantation?
Used by oocyte during oogenesis (starts to degrade during ovulation), transitions to embryonic genome during the one or two cell stage (by zygote)
How is the maternal RNA produced? What might they encode?
1) Produced normally, but is deadenylated.
2) Maskin protein binds and preserves the RNA until it is needed.
3) When needed, Maskin is removed and poly A tail is added
4) it can now be transcribed
-lots of machinery encoded to prepare for activation of embryonic genome
What is responsible for maternal RNA degradation?
miRNA that utilizes dicer protein
How can miRNA and RISC affect mRNA?
- can degrade or interact with other proteins to protect RNA
- miRNA can bind to regulate growth factors
- miRNA has role in regulation of growth (defect associated with some cancers)
Summarize early developmental regulation
1) Early developmental cleavage divisions are controlled by maternal mRNAs stored in the egg during oogenesis (“autopilot”)
2) Translation of Maternal mRNAs is regulated by mechanisms that control polyadenylation (Maskin prevents translation until needed)
3) Activation of the zygotic genome doesn’t occur until the 4-cell stage in human embryos (gradual process)
4) Maternal mRNAs may be degraded by the RISC complex acting in conjunction with specific miRNAs (feedforward activity)
In order to allow transcription factors into the DNA, histones must be ___________ through ____________
unraveled through modifications (markings)
-ex. methylated lysines, acetylated lysines, or phosphorylated serines
Why have histone modifications?
You can go from ‘active’ or ‘open’ chromatin to allow transcription factors to turn on/off genes OR
‘silent’ chromatin to shut down gene expression
REMEMBER: many diff marks and can have different functions
What happens in terms of histone modification during the transition from pluripotent and differentiation?
A pluripotent and differentiated cell will have lots of genes ON and OFF
What genes might be turned off in a germ cell?
Specialized genes that differentiate a cell
How is zygotic genome regulated?
1) Dynamic changes in gene expression occur during development as specific lineages are established.
2) Activation or repression of genes is controlled by changes in the chromatin state that affect the ability of the transcriptional machinery to access genes.
3) Changes in the chromatin state are mainly brought about through histone modifications.
4) A histone “code” likely instructs or allows specific transcription factors to access genes to turn them on in a lineage- or cell type-specific manner.
How are genes regulated for:
1) pluripotent -> differentiated
2) pluripotent -> germ cell
PRC containing PcG protein can temporarily silence genes so that it isn’t shut off long term (ie. pluripotent needs genes turned off but turned back on once it is differentiated), (differentiated cell won’t need pluripotent genes so those can be methylated to turn it off long term), (germ cells need their genes, so pluripotency only turned off temporarily by PRC containing PcG)
How are paternal and maternal genomes regulated?
Imprinting
Describe genomic imprinting
1) An epigenetic process by which certain genes are expressed in a parental-specific manner
2) Involves methylation and histone modifications
3) Imprinted alleles are silenced so that the gene which is expressed only comes from the mother or the father
4) Modifications are maintained in all cells of the organism
5) Regulated expression of imprinted genes is vital for normal development
Describe example of Igf2 imprinting.
Igf2 interacts with Igf2 receptor
1) in mom: Igf2 receptor ON, Igf2 OFF
2) in dad: Igf2 receptor OFF, Igf2 ON
3) if we delete mothers Igf2 receptor, we get LARGE offspring
4) if we delete fathers Igf2, we get DWARF offspring
5) if we delete mothers Igf2 receptor and fathers Igf2, we get normal sized offspring (they compensate)
How is a gene silenced? (imprinted)
DNA methylation turns gene expression OFF
You can imprint single genes or an entire region
