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Ch. 19 - Epigenetics

Chapter 18, Problem 24

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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Hi everyone welcome back. Here's our next question. Gamma Globe in is expressed during fetal development but become silenced in adults due to methylation of side iodine in a CPG island in or near the promoter. Which of the following do you believe will stimulate its expression in adult patients if incorporated into DNA. So we have the expression of a gene that's expressed in fetal development, silenced and adults by methylation. So the addition of a methyl group of sighting. So our question says what then would be most likely to cause the expression to be stimulated in adult patients if it's incorporated into their DNA. And we've got four different answer choices with four different chemicals here. Or compounds choice A €50 ill be five sided in C. Two amino peering and D. A. Cycle iguanas seen. Well, since our silencing occurs by the methylation of cytosine, that leads us to the correct answer here, which is choice B. Five as a sideline. And that's because this is a sighting analog that can't be methylated. So if you incorporate that into the adults, D. N. A. Since the the mechanism silencing is meth relating aside indian residue. If you've got this analog incorporated in the D. N. A. That can't be methylated, you have the most likelihood of causing expression of this gene in adult patients. Since the silent silencing mechanism will no longer work. So let's just quickly look at our other answer choices choice A €5 ill. Um Not our answer choices of a euros L. Analog. It can substitute for thinning and D. N. A. And gets used as an artificial mutation and scientific experiments but not our answer choice since it's not going to be likely to cause this expression in adult patients. Since it's an analog €2 ill and not going to affect that methylation of sitting Choice C. is two amino pureeing and this gets used as a fluorescent marker for D. N. A. Actually. Um It's an analog, an artificial analog of guanine and adenine as this being this. Oops okay, there we go. We're adding that in the wrong place to amino pureeing is an analog of guanine. Adami gets used as a fluorescent marker. It compare with timing. Um It also gets used as an artificial mutation but not what we're looking for since it's not an analog of the cited in here. So I see, not correct. And finally a cyclo guana seen as we can see by looking at the name here as its name indicates. It's a guana zine analog and interestingly is a medication for HSV or herpes and that's because it interferes in substituting here with the action of HSV. D. N. A. Prelim race so prevents the um inc generation of the D. N. A. From that retrovirus that will incorporate into the cell's DNA. So it's kind of interesting little note there but not the answer we're looking for. So again we've got gamma globe in as expressed during fetal development will become silenced and adults do the methylation of cytosine which the following do you believe will stimulate its expression in adult patients if incorporated into DNA. And that's just B5 is a sight to see you in the next video.
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Amino acids are classified as positively charged, negatively charged, or electrically neutral.

Which category includes lysine?

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

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

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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.

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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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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