Examples of histone modifications are acetylation (by histone acetyltransferase, or HAT), which is often linked to gene activation, and deacetylation (by histone deacetylases, or HDACs), which often leads to gene silencing typical of heterochromatin. Such heterochromatinization is initiated from a nucleation site and spreads bidirectionally until encountering boundaries that delimit the silenced areas. In the brief discussion of position effect, where repositioning of the w⁺ allele in Drosophila by translocation or inversion near heterochromatin produces intermittent w⁺ activity. In the heterozygous state (w⁺/w) a variegated eye is produced, with white and red patches. How might one explain position-effect variegation in terms of histone acetylation and/or deacetylation?

It has been shown that infectious agents such as viruses often exert a dramatic effect on their host cell's genome architecture. In many cases, viruses induce methylation of host DNA sequences in order to enhance their infectivity. What specific host gene functions would you consider as strong candidates for such methylation by infecting viruses?
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Key Concepts
DNA Methylation
Host Gene Functions
Viral Manipulation of Host Genomes
Contrast the structure of SINE and LINE DNA sequences. Why are LINEs referred to as retrotransposons?
Variable number tandem repeats (VNTRs) are repeating DNA sequences of about 15–100 bp in length, found both within and between genes. Why are they commonly used in forensics?
Cancer can be defined as an abnormal proliferation of cells that defy the normal regulatory controls observed by normal cells. Recently, histone deacetylation therapies have been attempted in the treatment of certain cancers [reviewed by Delcuve et al. (2009)]. Specifically, the FDA has approved histone deacetylation (HDAC) inhibitors for the treatment of cutaneous T-cell lymphoma. Explain why histone acetylation might be associated with cancer and what the rationale is for the use of HDAC inhibitors in the treatment of certain forms of cancer.
While much remains to be learned about the role of nucleosomes and chromatin structure and function, recent research indicates that in vivo chemical modification of histones is associated with changes in gene activity. One study determined that acetylation of H3 and H4 is associated with 21.1 percent and 13.8 percent increases in yeast gene activity, respectively, and that histones associated with yeast heterochromatin are hypomethylated relative to the genome average [Bernstein et al. (2000)]. Speculate on the significance of these findings in terms of nucleosome–DNA interactions and gene activity.
