RUNNING OUT OF TIME PLEASE HELP ANSWER THE QUESTION BELOW Article reading #3: From an article entitled “The Role of Meth

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RUNNING OUT OF TIME PLEASE HELP ANSWER THE QUESTION BELOW
Article reading #3: From an article entitled “The Role
of Methylation in Gene
Expression”
5-azacytidine Experiments Provide Early Clues to the Role
of Methylation in Gene
Expression
There are many ways that gene expression is controlled in
eukaryotes, but
methylation of DNA (not to be confused with histone methylation) is
a common
epigenetic signaling tool that cells use to lock genes in the "off"
position. In recent
decades, researchers have learned a great deal about DNA
methylation, including how it
occurs and where it occurs....
Prior to 1980, there were a number of clues that suggested that
methylation might
play a role in the regulation of gene expression. For example, J.
D. McGhee and G. D.
Ginder compared the methylation status of the beta-globin locus in
cells that did and did
not express this gene. Using restriction enzymes that distinguished
between methylated
and unmethylated DNA, the duo showed that the beta-globin locus was
essentially
unmethylated in cells that expressed beta-globin but methylated in
other cell types
(McGhee & Ginder, 1979). This and other evidence of the time
were indirect suggestions
that methylation was somehow involved in gene expression.
Shortly after McGhee and Ginder published their results, a more
direct
experiment that examined the effects of inhibiting methylation on
gene expression was
performed using 5-azacytidine in mouse cells. 5-azacytidine is one
of many chemical
analogs for the nucleoside cytidine. When these analogs are
integrated into growing DNA
strands, some, including 5-azacytidine, severely inhibit the action
of the DNA
methyltransferase enzymes that normally methylate DNA.
(Interestingly, other analogs,
like Ara-C, do not negatively impact methylation.)
Because most DNA methylation was known to occur on cytosine
residues,
scientists hypothesized that if they inhibited methylation by
flooding cellular DNA with
5-azacytidine, then they could compare cells before and after
treatment to see what
impact the loss of methylation had on gene expression. Knowing that
gene expression
changes are responsible for cellular differentiation, these
researchers used changes in
cellular phenotypes as a proxy for gene expression changes (Table
1)
Table 1: Effect of Cytidine Analogs on Cell Differentiation
and DNA Methylation
According to this article, when the nucleotide cytosine is
replaced with a chemical analog of cytidine in a strand of DNA
A. methylation is always blocked.
B. methylation is blocked when certain chemical analogs of
cytidine are used, but not when other analogs are used.