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Ch. 19 - Epigenetics
Chapter 18, Problem 24

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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span>Understand the role of histone methylation: Histone methylation is a type of epigenetic modification that can either activate or repress gene expression depending on the specific histone and lysine residue that is methylated.</span
span>Identify the specific histone modifications: H3K9 methylation is generally associated with gene silencing, while methylation of H3K4 and H4K20 is often linked to gene activation.</span
span>Consider the combination of modifications: The presence of multiple methylation marks (H3K9, H3K4, and H4K20) suggests a complex regulatory mechanism where the combination of these marks can lead to different transcriptional outcomes.</span
span>Analyze the potential interactions: The combination of these methylation marks might create a unique chromatin environment that is recognized by specific proteins or complexes that can either activate or repress transcription.</span
span>Draw conclusions: The presence of H3K4 and H4K20 methylation alongside H3K9 methylation indicates that the overall effect on transcription is context-dependent, and the combination of these marks can override the silencing effect of H3K9 methylation alone, leading to gene activation.</span

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Key Concepts

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

Histone Methylation

Histone methylation is a post-translational modification where methyl groups are added to specific amino acids on histone proteins. This process can influence gene expression by altering chromatin structure, either promoting or repressing transcription. The specific effects depend on which histone residues are methylated and the context of other modifications.
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Histone Protein Modifications

Transcriptional Regulation

Transcriptional regulation refers to the mechanisms that control the rate of gene expression. It involves various factors, including transcription factors, enhancers, and epigenetic modifications like histone methylation. The interplay between activating and repressing marks on histones can determine whether a gene is turned on or off, highlighting the complexity of gene regulation.
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Epigenetic Interactions

Epigenetic interactions involve the complex relationships between different epigenetic modifications, such as methylation and acetylation, that can influence gene expression. The presence of multiple modifications on histones can create a 'code' that determines the transcriptional outcome. For instance, the combination of H3K9 methylation (which silences) with H3K4 and H4K20 methylation (which activates) suggests a nuanced regulatory mechanism that can switch gene expression states.
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Related Practice
Textbook Question

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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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

DNA methylation is commonly associated with a reduction of transcription. The following data come from a study of the impact of the location and extent of DNA methylation on gene activity in eukaryotic cells. A bacterial gene, luciferase, was inserted into plasmids next to eukaryotic promoter fragments. CpG sequences, either within the promoter and coding sequence (transcription unit) or outside of the transcription unit, were methylated to various degrees, in vitro. The chimeric plasmids were then introduced into cultured cells, and luciferase activity was assayed. These data compare the degree of expression of luciferase with differences in the location of DNA methylation [Irvine et al. (2002). Mol. and Cell. Biol. 22:6689–6696]. What general conclusions can be drawn from these data? 


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