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Ch. 19 - Epigenetics
Chapter 18, Problem 23

Amino acids are classified as positively charged, negatively charged, or electrically neutral.

How does acetylation of lysine affect its interaction with DNA, and how is this related to the activation of gene expression?

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span>1. Understand the basic properties of lysine: Lysine is a positively charged amino acid due to its side chain, which contains an amino group that can accept a proton, giving it a positive charge at physiological pH.</span
span>2. Consider the interaction between lysine and DNA: DNA is negatively charged due to its phosphate backbone. The positive charge on lysine allows it to interact with the negatively charged DNA, often helping to stabilize the structure of chromatin.</span
span>3. Explore the process of acetylation: Acetylation is the addition of an acetyl group (CH<sub>3</sub>CO) to a molecule. In the case of lysine, acetylation occurs on the amino group of its side chain, neutralizing its positive charge.</span
span>4. Analyze the effect of acetylation on lysine-DNA interaction: When lysine is acetylated, its positive charge is neutralized, reducing its ability to interact with the negatively charged DNA. This can lead to a loosening of the chromatin structure.</span
span>5. Connect acetylation to gene expression: The loosening of chromatin structure due to acetylation of lysine residues on histones can make DNA more accessible to transcription factors and other proteins involved in gene expression, thereby facilitating the activation of gene expression.</span

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Key Concepts

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

Amino Acid Classification

Amino acids are organic compounds that serve as the building blocks of proteins. They can be classified based on their side chains into three categories: positively charged (basic), negatively charged (acidic), and electrically neutral (polar or nonpolar). This classification is crucial for understanding how amino acids interact with other molecules, including DNA.
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Acetylation

Acetylation is a post-translational modification where an acetyl group is added to a molecule, often a lysine residue in proteins. This modification can neutralize the positive charge of lysine, reducing its affinity for negatively charged DNA. Consequently, acetylation can influence the accessibility of DNA for transcription factors, thereby playing a significant role in gene expression regulation.
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Histone Protein Modifications

Gene Expression Regulation

Gene expression regulation refers to the processes that control the timing and amount of gene product (RNA or protein) produced in a cell. Modifications like acetylation can alter chromatin structure, making DNA more or less accessible for transcription. This dynamic regulation is essential for cellular responses to environmental signals and developmental cues.
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Related Practice
Textbook Question

From the data in Table 19.3, draw up a list of histone H3 modifications associated with gene activation. Then draw up a list of H3 modifications associated with repression.

If not, how can you reconcile these differences?

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Textbook Question

Amino acids are classified as positively charged, negatively charged, or electrically neutral.

Which category includes lysine?

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Textbook Question

Amino acids are classified as positively charged, negatively charged, or electrically neutral.

How does this property of lysine allow it to interact with DNA?

351
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Textbook Question

A particular type of anemia in humans, called β-thalassemia, results from a severe reduction or absence of the normal β-globin chain of hemoglobin. However, the γ-globin chain, normally only expressed during fetal development, can functionally substitute for β-globin. A variety of studies have explored the use of the nucleoside 5-azacytidine for the expression of γ-globin in adult patients with β-thalassemia.

Explain why this drug may also have some adverse side effects.

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Textbook Question

A particular type of anemia in humans, called β-thalassemia, results from a severe reduction or absence of the normal β-globin chain of hemoglobin. However, the γ-globin chain, normally only expressed during fetal development, can functionally substitute for β-globin. A variety of studies have explored the use of the nucleoside 5-azacytidine for the expression of γ-globin in adult patients with β-thalassemia.

How might 5-azacytidine lead to expression of γ-globin in adult patients?

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Textbook Question

Methylation of H3K9 by itself silences genes, but if H3K4 and H4K20 are also methylated, the combination of modifications stimulates transcription. What conclusions can you draw about this?

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