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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 21

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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1
Understand the role of histones in nucleosome structure: Histones are proteins that help package DNA into nucleosomes, forming chromatin. Their chemical modifications, such as acetylation and methylation, influence how tightly DNA is wrapped around them, affecting gene accessibility.
Analyze the impact of acetylation on histones: Acetylation of histones H3 and H4 reduces the positive charge on histones, weakening their interaction with negatively charged DNA. This loosening of DNA allows transcription machinery easier access to genes, increasing gene activity.
Interpret the significance of hypomethylation in heterochromatin: Methylation typically leads to tighter chromatin packing and gene silencing. Hypomethylation in yeast heterochromatin suggests a less condensed structure, potentially allowing for some gene activity in regions that are usually transcriptionally inactive.
Connect findings to gene regulation: The study highlights how chemical modifications of histones, such as acetylation and methylation, serve as epigenetic markers that regulate gene activity by altering chromatin structure and nucleosome-DNA interactions.
Speculate on broader implications: These findings suggest that histone modifications are key mechanisms for dynamic gene regulation, allowing cells to respond to environmental changes or developmental cues by modulating chromatin accessibility and gene expression.

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Key Concepts

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

Nucleosomes

Nucleosomes are the fundamental units of chromatin, consisting of a segment of DNA wrapped around a core of histone proteins. This structure helps package DNA into a compact form, allowing it to fit within the cell nucleus. The arrangement and modification of nucleosomes play a crucial role in regulating access to DNA, thereby influencing gene expression.
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Histone Modifications

Histone modifications, such as acetylation and methylation, are chemical changes to the histone proteins that can alter chromatin structure and function. Acetylation typically leads to a more open chromatin configuration, promoting gene activation, while methylation can either activate or repress gene expression depending on the specific context. These modifications serve as signals that can recruit other proteins to regulate transcription.
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Guided course
07:55
Histone Protein Modifications

Chromatin Structure and Gene Activity

The structure of chromatin, which can exist in a more condensed (heterochromatin) or relaxed (euchromatin) state, directly impacts gene activity. Changes in chromatin structure, influenced by histone modifications, can either facilitate or hinder the binding of transcription factors and RNA polymerase to DNA, thus regulating the transcription of genes. Understanding these dynamics is essential for elucidating how genes are turned on or off in response to various cellular signals.
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Related Practice
Textbook Question

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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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

An article entitled 'Nucleosome Positioning at the Replication Fork' states: 'both the 'old' randomly segregated nucleosomes as well as the 'new' assembled histone octamers rapidly position themselves (within seconds) on the newly replicated DNA strands' [Lucchini et al. (2002)]. Given this statement, how would one compare the distribution of nucleosomes and DNA in newly replicated chromatin? How could one experimentally test the distribution of nucleosomes on newly replicated chromosomes?

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Textbook Question

The human genome contains approximately 106 copies of an Alu sequence, one of the best-studied classes of short interspersed elements (SINEs), per haploid genome. Individual Alu units share a 282-nucleotide consensus sequence followed by a 3'-adenine-rich tail region [Schmid (1998)]. Given that there are approximately 3 x 109 base pairs per human haploid genome, about how many base pairs are spaced between each Alu sequence?

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Textbook Question

The following is a diagram of the general structure of the bacteriophage chromosome. Speculate on the mechanism by which it forms a closed ring upon infection of the host cell.

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