Gene regulation in eukaryotes II: Epigenetics - Epigenetics and development

21 important questions on Gene regulation in eukaryotes II: Epigenetics - Epigenetics and development

Which property of cells in the adult leads to the results of X-chromosome inactivation, the formation of specific cell types and genomic imprinting?

Adult cells 'remember' events that happened during embryonic development.

Which 2 regions in the DNA in the vicinity of the gene H19 and Igf2 can be methylated?

The imprinting control region (ICR) and the differentially methylated region (DMR).

What happens when a loop forms in the DNA with the expression of the genes Igf2 and H19?

The enhancer is not able to stimulate Igf2, and the maternal allele is turned off.
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During which process does CTCF bind to both ICR and DMR, so that Igf2 is not expressed?

During oogenesis.

During which process are ICR and DMR methylated?

During spermatogenesis.

What happens when ICR and DMR are methylated?

CTCFs are unable to bind to these sites, so the enhancer stimulates the Igf2 gene.

By which process is the methylation pattern in the sperm cells maintained in the somatic cells of offspring?

Maintenance methylation, the methylation of hemimethylated sites.

What does XCI achieve?

Dosage compensation.

Which region in the X-chromosome plays a key role in XCI?

The X-inactivation center (Xic).

Which proteins play a role in the pairing of the two X chromosomes?

Pluripotency factors and CTCFs.

What happens when the two X chromosomes are paired?

Pluripotency factors and CTCFs shift to one of the X chromosomes, which will express the Tsix gene and become active. The other X chromosome will express Xist and become inactive.

What happens after the pluripotency factors and CTCFs have shifted to one X chromosome?

On the inactive X chromosome (Xi), a tethering ('vastbinden') protein binds to repeat C within Xist RNA, so that the Xist RNA becomes bound to the Xic.

How does the spreading phase on the inactive X chromosome begin?

- The Xist RNAs bind to each othre and to a DNA-binding protein called hnRNP-U;
- The hnRNP-Us (with Xist RNAs) bind to numerous AT-rich regions within the inactive X chromosome DNA.

What happens after the spreading phase (3 events)?

- Xist RNA recruits protein complexes to Xi, which cause covalent modifications of specific sites in histone tails.
- Histone variant macroH2A is incorporated into nucleosomes at many sites.
- Recruitment of DNA methyltransferases to Xi, which leads to DNA methylation.

To what do these 3 events lead?

To the silencing of the genes on Xi and its compaction into a Barr body.

Which of these complexes is involved with gene activation, and which is involved with gene repression?

TrxG complexes cause gene activation, and PcG complexes cause gene repression.

TrxG and PcG complexes regulate many different genes, but what kind of genes do they particularly regulate?

Genes that encode transcription factors that control developmental changes and cell differenatiation.

What is an important way in which TrxG and PcG complexes perform gene regulation?

Covalent modification of histones.

To what in the DNA do PRC1 and PCR2 bind?

Polycomb response element (PRE).

How do polycomb group complexes do epigenetic silencing of a gene (steps)?

- A PRE-binding protein binds to the PRE and recruits PRC2 to the site;
- PRC2 catalyzes the attachment of 3 methyl groups onto lysine 27 of histone H3;
- Trimethylation of lysine 27 
  • Directly inhibits transcription, or
  • Recruits PRC1 to the target gene, which inhibits transcription by
    • Chromatin compaction;
    • Covalent modification of histones;
    • Direct interaction with a transcription factor.

How are these epigenetic changes during embryonic development be transmitted to a population of cells that give rise to a particular type of tissue?

The changes are maintained during subsequent cell divisions.

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