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Ch. 12 - DNA Organization in Chromosomes
Klug - Concepts of Genetics  12th Edition
Klug12th EditionConcepts of Genetics ISBN: 9780135564776Not the one you use?Change textbook
Chapter 12, Problem 18

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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Understand the context: Viruses can manipulate the host genome to enhance their infectivity. DNA methylation is a common epigenetic modification that silences gene expression. Consider which host genes, if silenced, would benefit the virus.
Identify host genes involved in immune response: Genes that regulate the host's antiviral defense mechanisms, such as interferon-stimulated genes (ISGs), are strong candidates for methylation. Silencing these genes would weaken the host's ability to fight the infection.
Consider genes involved in apoptosis: Apoptosis, or programmed cell death, is a defense mechanism that prevents viral replication. Viruses may methylate genes that promote apoptosis, such as *TP53* (p53), to keep the host cell alive and allow viral replication.
Evaluate genes regulating cell cycle control: Viruses often hijack the host's cell cycle machinery to promote their replication. Methylation of tumor suppressor genes like *RB1* (retinoblastoma protein) or *CDKN2A* (p16) could disrupt cell cycle checkpoints, favoring viral replication.
Think about genes involved in DNA repair: Methylation of DNA repair genes, such as *BRCA1* or *MLH1*, could increase genomic instability, which might benefit the virus by creating a more permissive environment for its replication and integration into the host genome.

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Key Concepts

Here are the essential concepts you must grasp in order to answer the question correctly.

DNA Methylation

DNA methylation is a biochemical process involving the addition of a methyl group to the DNA molecule, typically at cytosine bases. This modification can regulate gene expression by silencing genes, thereby influencing various cellular functions. In the context of viral infections, viruses may exploit this mechanism to alter host gene expression, enhancing their own infectivity.
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Host Gene Functions

Host gene functions refer to the roles played by genes within the host organism that are crucial for maintaining cellular processes, such as immune response, cell cycle regulation, and apoptosis. Viruses may target specific host genes that are involved in these processes to evade immune detection or promote viral replication, making them prime candidates for methylation.
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Viral Manipulation of Host Genomes

Viral manipulation of host genomes involves strategies employed by viruses to alter the genetic and epigenetic landscape of their host cells. This can include the induction of methylation changes that suppress host defenses or promote a favorable environment for viral replication. Understanding these interactions is essential for identifying which host genes are likely to be affected during viral infections.
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Related Practice
Textbook Question

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?

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Textbook Question

Contrast the structure of SINE and LINE DNA sequences. Why are LINEs referred to as retrotransposons?

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Textbook Question

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?

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Textbook Question

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.

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Textbook Question
In a study of Drosophila, two normally active genes, w⁺ (wild-type allele of the white-eye gene) and hsp26 (a heat-shock gene), were introduced (using a plasmid vector) into euchromatic and heterochromatic chromosomal regions, and the relative activity of each gene was assessed [Sun et al. (2002)]. An approximation of the resulting data is shown in the following table. Which characteristic or characteristics of heterochromatin are supported by the experimental data?Gene Activity (relative percentage) _Euchromatin Heterochromatinhsp26 100% 31%w⁺ 100% 8%
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Textbook Question

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.

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