it and answer the following questions. Recent studies showing a correlation between the levels of DNA (cytosine-5-)- methyltransferase (DNA MTase) enzyme activity and tumorigenicity have implicated this enzyme in the carcinogenic process. Moreover, hypermethylation of CpG island-containing promoters is associated with the inactivation of genes important to tumor initiation and progression. One proposed role for DNA MTase in tumorigenesis is therefore a direct role in the de novo methylation of these otherwise unmethylated CpG islands. In this study, we sought to determine whether increased levels of DNA MTase could directly affect CpG island methylation. A full-length CDNA for human DNA MTase driven by the cytomegalovirus promoter was constitutively expressed in human fibroblasts. Individual clones derived from cells transfected with DNA MTase (HMT) expressed 1- to 50-fold the level of DNA MTase protein and enzyme activity of the parental cell line or clones transfected with the control vector alone (Neo). To determine the effects of DNA MTase overexpression on CpG island methylation, we examined 12 endogenous CpG island loci in the HMT clones. HMT clones expressing > or = 9-fold the parental levels of DNA MTase activity were significantly hypermethylated relative to at least 11 Neo clones at five CpG island loci. In the HMT clones, methylation reached nearly 100% at susceptible CpG island loci with time in culture. In contrast, there was little change in the methylation status in the Neo clones over the same time frame. Taken together, the data indicate that overexpression of DNA MTase can drive the de novo methylation of susceptible CpG island loci, thus providing support for the idea that DNA MTase can contribute to tumor progression through CpG island methylation-mediated gene inactivation. a. What are the structures of cytosine and 5-methylcytosine? b. What are CpG islands? Draw a CpG group. c. What are promoters? d. What does 'transfection’ mean? e. What are 'single clones' and how did various single clones differ?

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1. Below is the abstract from a journal article "De novo methylation of CpG island sequences in
human fibroblasts overexpressing DNA (cytosine-5-)-methyltransferase" by Vertino et al. Read
it and answer the following questions.
Recent studies showing a correlation between the levels of DNA (cytosine-5-)-
methyltransferase (DNA MTase) enzyme activity and tumorigenicity have implicated this
enzyme in the carcinogenic process. Moreover, hypermethylation of CpG island-containing
promoters is associated with the inactivation of genes important to tumor initiation and
progression. One proposed role for DNA MTase in tumorigenesis is therefore a direct role in the
de novo methylation of these otherwise unmethylated CpG islands. In this study, we sought to
determine whether increased levels of DNA MTase could directly affect CpG island methylation.
A full-length CDNA for human DNA MTase driven by the cytomegalovirus promoter was
w ww
constitutively expressed in human
bro
lasts. Individual clones derived from cells transfected
with DNA MTase (HMT) expressed 1- to 50-fold the level of DNA MTase protein and enzyme
activity of the parental cell line or clones transfected with the control vector alone (Neo). To
determine the effects of DNA MTase overexpression on CpG island methylation, we examined
12 endogenous CpG island loci in the HMT clones. HMT clones expressing > or = 9-fold the
parental levels of DNA MTase activity were significantly hypermethylated relative to at least 11
Neo clones at five CpG island loci. In the HMT clones, methylation reached nearly 100% at
susceptible CpG island loci with time in culture. In contrast, there was little change in the
methylation status in the Neo clones over the same time frame. Taken together, the data
indicate that overexpression of DNA MTase can drive the de novo methylation of susceptible
CpG island loci, thus providing support for the idea that DNA MTase can contribute to tumor
w
progression through CpG island methylation-mediated gene inactivation.
a. What are the structures of cytosine and 5-methylcytosine?
b. What are CpG islands? Draw a CpG group.
c. What are promoters?
d. What does 'transfection' mean?
e. What are 'single clones' and how did various single clones differ?
f. What is the main conclusion of the paper?
Transcribed Image Text:1. Below is the abstract from a journal article "De novo methylation of CpG island sequences in human fibroblasts overexpressing DNA (cytosine-5-)-methyltransferase" by Vertino et al. Read it and answer the following questions. Recent studies showing a correlation between the levels of DNA (cytosine-5-)- methyltransferase (DNA MTase) enzyme activity and tumorigenicity have implicated this enzyme in the carcinogenic process. Moreover, hypermethylation of CpG island-containing promoters is associated with the inactivation of genes important to tumor initiation and progression. One proposed role for DNA MTase in tumorigenesis is therefore a direct role in the de novo methylation of these otherwise unmethylated CpG islands. In this study, we sought to determine whether increased levels of DNA MTase could directly affect CpG island methylation. A full-length CDNA for human DNA MTase driven by the cytomegalovirus promoter was w ww constitutively expressed in human bro lasts. Individual clones derived from cells transfected with DNA MTase (HMT) expressed 1- to 50-fold the level of DNA MTase protein and enzyme activity of the parental cell line or clones transfected with the control vector alone (Neo). To determine the effects of DNA MTase overexpression on CpG island methylation, we examined 12 endogenous CpG island loci in the HMT clones. HMT clones expressing > or = 9-fold the parental levels of DNA MTase activity were significantly hypermethylated relative to at least 11 Neo clones at five CpG island loci. In the HMT clones, methylation reached nearly 100% at susceptible CpG island loci with time in culture. In contrast, there was little change in the methylation status in the Neo clones over the same time frame. Taken together, the data indicate that overexpression of DNA MTase can drive the de novo methylation of susceptible CpG island loci, thus providing support for the idea that DNA MTase can contribute to tumor w progression through CpG island methylation-mediated gene inactivation. a. What are the structures of cytosine and 5-methylcytosine? b. What are CpG islands? Draw a CpG group. c. What are promoters? d. What does 'transfection' mean? e. What are 'single clones' and how did various single clones differ? f. What is the main conclusion of the paper?
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