Read the summary and the most important questions on 5.3 Epigenetics in Development | Jochem Louisse

• 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.