Question

1- A scientific study demonstrated that rat mothering behavior impacts the stress response in their pups. Rats that were born and grew up with attentive mothers showed low activation of stress-response genes later in life, while rats with inattentive mothers had high activation of stress-response genes in the same situation. An additional study that swapped the pups at birth (i.e., rats born to inattentive mothers grew up with attentive mothers and vice versa) showed the same positive effect of attentive mothering. How do genetics and/or epigenetics explain the results of this study?

2- Some autoimmune diseases show a positive correlation with dramatically decreased expression of histone deacetylase 9 (HDAC9, an enzyme that removes acetyl groups from histones). Why would the decreased expression of HDAC9 cause immune cells to produce inflammatory genes at inappropriate times?

3- A scientist identifies a potential transcription regulation site 300bp downstream of a gene and hypothesizes that it is a repressor. What experiment (with results) could he perform to support this hypothesis?

4- A scientist discovers a virus encoding a Protein X that degrades a subunit of the eIF4F complex. Knowing that this virus transcribes its own mRNAs in the cytoplasm of human cells, why would Protein X be an effective virulence factor?

Answer 1

1. Answer : Pups swapping at the birth indicates that the genes inherited from the attentive or inattentive mothers does not explain the rats stress responses in their later life. But instead, the researchers had found that attentive mothering caused the methylation of genes which controls the expression of stress receptors in the brain. Hence, rats those received attentive maternal care exhibited epigenetic changes which limited the expression of stress-response genes, and that the effect was durable over their lifespans.

2. Answer : The histone acetylation reduces positive charge of histone proteins, thereby loosening the DNA which is wrapped around the histones. This loosened DNA then can interact with the transcription factors to express genes found at that region. In normal, once the gene is no longer needed, the histone deacetylase enzymes remove the acetyl groups from histones by which the DNA becomes tightly wound and inaccessible again. But when there is a defect in the HDAC9, deacetylation may not occur. In an immune cell, this would mean that the inflammatory genes which was made accessible during an infection are not tightly rewound around the histones.

3. Answer : One of the easiest experiment to test his hypothesis is to mutate the site in a cell, and monitor the levels of mRNA transcript made from the gene. If the results indicate increase in levels of transcript in the mutated cell, then the site was repressing the transcription.

4. Answer : The degrading of eIF4F complex prevents the pre-initiation complex (eIF-2-GTP, tRNAi-Met, and 40S ribosomal subunit) from being recruited into 5’ cap of the mature mRNAs in cell. This then allows the virus to hijack the translation machinery of human cells to translate its own mRNA transcripts instead.