Summary: 5.3 Epigenetics In Development | Jochem Louisse
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1 Embryonic Development
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.
What are the different stages of embronic stem cells in differentiation potential? (3)
zygote: totipotent; ICM/ES cells: pluripotent; somatic stem cells: multipotent
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
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.
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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