Summary: 5.3 Epigenetics In Development | Jochem Louisse
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1 Embryonic Development
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What are the first three stages of embryonic development?
1: fertilized human egg: zygote
2: solid ball of cells: morula
3: hollow ball of cells: blastocyst. With inner cell mass (ICM), which will form all tissue -
What are the differences between the paternal and maternal pronucleus (PN), and why?
pat PN: lacks histone modification (H3K9me2 and H3K27me3), loses 5-methylcytosine (5-MeC) on genome wide scale. mat PN: has both. Oocyte genome is transcriptionally inactive, but maternally inherited transcripts and proteins are needed for the first cleavages.
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What are the different stages of embronic stem cells in differentiation potential? (3)
zygote: totipotent; ICM/ES cells: pluripotent; somatic stem cells: multipotent
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What are the three germ layers, and what tissue do they form?
1. endoderm: GI tract, lungs
2. mesoderm: muscle, bone, blood, urogenital tract
3. ectoderm: epidermal, nervous system -
How is pluripotency and differentiation epigenetically regulated?
pluripotency: epigenetic regulators and pluripotency factors activate pluripotency genes (via H3K4me3) and repress differentiation-genes (via H3K27me3).
differentiation: miRNAs downregulate pluripotency factors, specifically activated differentiation-gene groups lose repressive marks. -
2 X-chromosome Inactivation
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What is X-chromosome inactivation?
Occurs only in females, silencing of one X-chromosome. Allows dosage compensation in comparison to males, which only have one X-chromosome.
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How is X-chromosome inactivation regulated? (3)
1: first cleavage: paternal X-chromosome imprinted inactivation
2: after blastocyst formation: ICM reactivate paternal X-chromosome; trophoectoderm and primitive endoderm retain inactive paternal X-chromosome.
3: differentiattion ICM: stochastic inactivation of either one X-chromosome. -
What is the mechanism of X-chromosome inactivation in mice?
major regulator: Xist gene, lies in specific region on X-chromosome called X inactivation center (XIC).
Non-coding gene, expressed by inactive X-chrom., produces a RNA coating over inactive X-chrom.
Tsix gene is expressed from the active X-chrom, inhibits Xist expression from active X-chrom. -
What actions does the Xist RNA coating have? (3)
1: recruitment of histone variant macro H2A
2: H3 and H4 modification
3: promotes CpG methylation
All lead to gene silencing initiation and maintenance -
3 Genomic Imprinting
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What is the conflict of interest in embryonic development for the father and the mother?
Father: wants the mother to devote maximum resources towards embryonic growth.
Mother: want to conserve resources towards future births, without compromising the health of the current embryo.
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