Theme 3: Eukaryo/c Transcrip/onal
Regula/on
• 19.1 Chroma+n to Messenger RNA in Eukaryotes
• (Side Note): Even though all cells in the human body have the
same genome, gene regula<on differences lead to altered
proteomes which contributes to dis<nct differences in cellular
func<ons
◦ Example: Hepatocytes (i.e. red blood cells), muscle cells,
neurons and epithelial cells all have dis<nct func<ons due to
difference in cues received during development though they
all developed from the same embryonic stem cells
• I.e. It is specific gene expression paGerns that are
triggered within dividing embryonic stem cells and
extracellular cues that lead to diversity of specialized
cells
▪ Note: Gene expression can change throughout
development of a cell
• 19.1.1 Gene expression can be influenced by chemical
modifica+on of DNA or histones.
◦ 1st level of control is at the chromosome (before
transcrip<on occurs)
◦ Note: Phosphoryla<on is oMen of serine and threonine
◦ Methyla<on oMen occurs in cytosine bases that are
adjacent to guanosine bases on a DNA strand
• Such pairs of nucleo<des are abbreviated “CpG” (the
“p” represents the phosphate in the backbone of the
DNA strand between the two nucleo<des)
• CpG Island: In mammalian protein-coding genes; CpG
sites clustered in small regions located in or near the
promoter
, • Some CpG site are methylated and some aren't
▪ Methylated CpG sites are rarely seen in CpG
islands near ac<ve genes (a.)
▪ Transcrip<onal repression of a gene is oMen
accompanied by heavy methyla<on of a nearby
CpG island (b.)
• Repression oMen due to RNA polymerase
and transcrip<on factors no longer being
able to bind to DNA
• BUT, some proteins (including
histone deacetylases (HDAC) which
promotes removal of acetyl groups
from neighbouring histones) only
bind to methylated DNA
• The methyla<on state of a CpG island can change over
<me/in response to environmental cues, providing a
way to turn genes on or off
• To prevent the expression of genes in viruses and
transposable elements, cells can heavily methylate
CpG islands of transposable elements/viral DNA
sequences
▪ Example: Cancer cells have methylated CpG
islands in the genome which represses genes
that could restrict cell growth
◦ Note: + symbol means transcrip<on is ac<vated and -
symbol means transcrip<on is repressed
◦ Chroma+n gives chromosomes their structure
• It includes a thread of nucleosome par<cles in which
about 150 base pairs of DNA are wrapped around
each octamer of histone proteins
◦ When chroma<n is in its coiled state, DNA is not accessible
to the proteins that carry out transcrip<on
◦ Chroma<n Remodeling: Nucleosomes are reposi<oned to
expose different stretches of DNA to the nuclear
environment (par<cularly transcrip<onal enzymes and
proteins)
Regula/on
• 19.1 Chroma+n to Messenger RNA in Eukaryotes
• (Side Note): Even though all cells in the human body have the
same genome, gene regula<on differences lead to altered
proteomes which contributes to dis<nct differences in cellular
func<ons
◦ Example: Hepatocytes (i.e. red blood cells), muscle cells,
neurons and epithelial cells all have dis<nct func<ons due to
difference in cues received during development though they
all developed from the same embryonic stem cells
• I.e. It is specific gene expression paGerns that are
triggered within dividing embryonic stem cells and
extracellular cues that lead to diversity of specialized
cells
▪ Note: Gene expression can change throughout
development of a cell
• 19.1.1 Gene expression can be influenced by chemical
modifica+on of DNA or histones.
◦ 1st level of control is at the chromosome (before
transcrip<on occurs)
◦ Note: Phosphoryla<on is oMen of serine and threonine
◦ Methyla<on oMen occurs in cytosine bases that are
adjacent to guanosine bases on a DNA strand
• Such pairs of nucleo<des are abbreviated “CpG” (the
“p” represents the phosphate in the backbone of the
DNA strand between the two nucleo<des)
• CpG Island: In mammalian protein-coding genes; CpG
sites clustered in small regions located in or near the
promoter
, • Some CpG site are methylated and some aren't
▪ Methylated CpG sites are rarely seen in CpG
islands near ac<ve genes (a.)
▪ Transcrip<onal repression of a gene is oMen
accompanied by heavy methyla<on of a nearby
CpG island (b.)
• Repression oMen due to RNA polymerase
and transcrip<on factors no longer being
able to bind to DNA
• BUT, some proteins (including
histone deacetylases (HDAC) which
promotes removal of acetyl groups
from neighbouring histones) only
bind to methylated DNA
• The methyla<on state of a CpG island can change over
<me/in response to environmental cues, providing a
way to turn genes on or off
• To prevent the expression of genes in viruses and
transposable elements, cells can heavily methylate
CpG islands of transposable elements/viral DNA
sequences
▪ Example: Cancer cells have methylated CpG
islands in the genome which represses genes
that could restrict cell growth
◦ Note: + symbol means transcrip<on is ac<vated and -
symbol means transcrip<on is repressed
◦ Chroma+n gives chromosomes their structure
• It includes a thread of nucleosome par<cles in which
about 150 base pairs of DNA are wrapped around
each octamer of histone proteins
◦ When chroma<n is in its coiled state, DNA is not accessible
to the proteins that carry out transcrip<on
◦ Chroma<n Remodeling: Nucleosomes are reposi<oned to
expose different stretches of DNA to the nuclear
environment (par<cularly transcrip<onal enzymes and
proteins)
