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Each somatic cell in the body generally contains the same DNA. A few
exceptions include red blood cells, which contain no DNA in their mature
state, and some immune system cells that rearrange their DNA while
producing antibodies. In general, however, the genes that determine whether
you have green eyes, brown hair, and how fast you metabolize food are the
same in the cells in your eyes and your liver, even though these organs
function quite differently. If each cell has the same DNA, how is it that cells or
organs are different? Why do cells in the eye differ so dramatically from cells
in the liver ?
Whereas each cell shares the same genome and DNA sequence, each cell
does not turn on, or express, the same set of genes. Each cell type needs a
the proteins to be expressed, the DNA must be transcribed into RNA and
the RNA must be translated into protein. In a given cell type, not all genes
encoded in the DNA are transcribed into RNA or translated into protein
proteins that make up the eye (iris, lens, and cornea) are only expressed in
the eye, whereas the specialized proteins in the heart (pacemaker cells,
heart muscle, and valves) are only expressed in the heart. At any given time,
only a subset of all of the genes encoded by our DNA are expressed and
regulated process with many levels and stages of control. This complexity
ensures the proper expression in the proper cell at the proper time.
In this section, you will learn about the various methods of gene regulation
and the mechanisms used to control gene expression, such as: epigenetic,
how a gene codes for a functional protein in a cell. The process occurs in both
therefore, their DNA floats freely within the cell cytoplasm. To synthesize a
primary method to control what type of protein and how much of each protein
transcriptional level.
Eukaryotic cells, in contrast, have intracellular organelles that add to their
complexity. In eukaryotic cells, the DNA is contained inside the cell's nucleus
transported out of the nucleus into the cytoplasm whereribosomes translate the
within the nucleus, and translation occurs only outside the nucleus within the
cytoplasm. The regulation of gene expression can occur at all stages of the
process . Regulation may occur when the DNA is uncoiled and loosened
is translated into protein (translational level), or after the protein has been
Bacteria such as E. coli need amino acids to survive. Tryptophan is one such
amino acid that E. coli can ingest from the environment. E. coli can also
synthesize tryptophan using enzymes that are encoded by five genes. These
five genes are next to each other in what is called the tryptophan (trp)
need to synthesize it; the switch controlling the activation of the genes in
the trp operon is turned off. However, when tryptophan availability is low,
the switch controlling the operon is turned on, transcription is initiated, the
A DNA sequence that codes for proteins is referred to as the coding region.
The five coding regions for the tryptophan biosynthesis enzymes are
coding region is the transcriptional start site. This is the region of DNA to
promoter region and the first trp-coding gene. This operator contains the
DNA code to which the repressor protein can bind. When tryptophan is
present in the cell, two tryptophan molecules bind to the trp repressor,
When tryptophan is not present in the cell, the repressor by itself does not
keep the genes turned off, the trp operon is negatively regulated and the
proteins that bind to the operator to silence trp expression are negative
regulators.
there are proteins that bind to the operator sequences that act as a positive
regulator to turn genes on and activate them. For example, when glucose is
scarce, E. coli bacteria can turn to other sugar sources for fuel. To do this,
new genes to process these alternate genes must be transcribed. This type
of process can be seen in the lac operon which is turned on in the presence
When glucose levels decline in the cell, accumulating cAMP binds to the
such as the lac operon. The CAP assists in production in the absence of
terminus, which is also responsible for the dimerization of the protein and a
DNA. This opens up the DNA molecule, allowing RNA polymerase to bind
and transcribe the genes involved in lactose catabolism. When cAMP binds
to CAP, the complex binds to the promoter region of the genes that are
required for transcription of the lac operon, this requirement reflects the
lactose.
A major type of gene regulation that occurs in prokaryotic cells utilizes and
occurs through inducible operons. Inducible operons have proteins that can
environment and the needs of the cell. The lac operon is a typical inducible
energy sources when glucose concentrations are low. To do so, the cAMP
One such sugar source is lactose. The lac operon encodes the genes
necessary to acquire and process the lactose from the local environment,
which includes the structural genes lacZ, lacY, and lacA. lacZ encodes -
CAP binds to the operator sequence upstream of the promoter that initiates
transcription of the lac operon. The lac operon uses a two-part control
However, for the lac operon to be activated, two conditions must be met.
First, the level of glucose must be very low or non-existent. Second, lactose
must be present. If glucose is absent, then CAP can bind to the operator
requirements is met, then transcription remains off. The cell can use lactose
lactose into glucose and galactose. Only when both conditions are satisfied
is the lac operon transcribed, such as when glucose is absent and lactose is
present . This process is beneficial and makes most sense for the cell as it
would be energetically wasteful to create the proteins to process lactose if
Genes are organized to make the control of gene expression easier. The
nucleotides long). The longer the promoter, the more available space for
proteins to bind. This also adds more control to the transcription process. The
genes. Consequently, the level of control of gene expression can also differ
Within the promoter region, just upstream of the transcriptional start site,
resides the TATA box. This box is simply a repeat of thymine and adenine
TFIIE, TFIIF, and TFIIH to the TATA box. Once this transcription initiation
phosphorylated. This releases part of the protein from the DNA to activate the
transcription initiation complex and places RNA polymerase in the correct
which can be quite a distance from the gene, in contact with transcription
factors bind to the promoters of a specific set of genes. They are not general
transcription factors that bind to every promoter complex, but are recruited to
acting elements because they are on the same chromosome, just next to the
gene. The region that a particular transcription factor binds to is called the
environmental stimuli that cause the proteins to find their binding sites and
transcription. These regions, called enhancers, are not necessarily close to the
genes they enhance. They can be located upstream of a gene, within the coding
region of the gene, downstream of a gene, or may be thousands of nucleotides
away.
changes. This shape change allows the interaction between the activators
the promoter region and the RNA polymerase to occur. Whereas DNA is
acetyl groups from lysine residues. This increases the positive charge on
histones, which strengthens the interaction between the histones and DNA,
it will fit into the nucleus. It is also organized so that specific segments can be
package and order DNA into structural units called nucleosome complexes,
which can control the access of proteins to the DNA regions. Under
proteins) can move along the string (DNA) and change the structure of
the nucleosomes surrounding that region of DNA can slide down the DNA to
open that specific chromosomal region and allow for the transcriptional
on signals found on both the histone proteins and on the DNA. These signals
are tags, or modifications, added to histone proteins and DNA that tell the
histones if a chromosomal region should be open or closed. These tags are not
specific amino acids in the protein or to the nucleotides of the DNA. The tags
do not alter the DNA base sequence, but they do alter how tightly wound the
therefore, changes in the charge of the histone will change how tightly wound
the DNA molecule will be. When unmodified, the histone proteins have a large
charge becomes less positive.The DNA molecule itself can also be modified.
This occurs within very specific regions called CpG islands. These are stretches
found in the promoter regions of genes. When this configuration exists, the
cytosine member of the pair can be methylated (a methyl group is added). This
modification changes how the DNA interacts with proteins, including the
parent to offspring, such that while the DNA sequence is not altered, the
The changes that occur to the histone proteins and DNA do not alter the
nucleotide sequence and are not permanent. Instead, these changes are
gene can be turned on or off depending upon the location and modifications to
RNA polymerase and other proteins, called transcription factors, to bind to the
promoter region, located just upstream of the gene, and initiate transcription.
If a gene is to remain turned off, or silenced, the histone proteins and DNA
RNA Splicing-
RNA splicing allows for the production of multiple protein isoforms from a
Information flows from DNA to RNA by the process of transcription and then
from RNA to protein by the process of translation. In order to ensure that the
gene contains extra sequences that do not code for protein. In these
splicing. The regions of RNA that code for protein are called exons . Splicing
process called alternative splicing. Alternative splicing allows more than one
Alternative Splicing-
Alternative splicing is a process that occurs during gene expression and allows
for the production of multiple proteins (protein isoforms) from a single gene
coding. Alternative splicing can occur due to the different ways in which an
exon can be excluded from or included in themessenger RNA. It can also occur
introns. For example, if a pre-mRNA has four exons (A, B, C, and D), these can
cis-acting sites that are found on the pre-RNA. Some of these regulatory
sites) and splicing repressors (proteins that reduce the use of certain sites).
in the sequence of their amino acids which results in altered function of the
protein. This is one reason why the human genome can encode a wide diversity
Spliceosome
The splicing of messenger RNA is accomplished and catalyzed by a macro-
molecule complex known as the spliceosome. The areas for ligation and
include the branch site (A) and the 5' and 3' splice sites. Interactions between
introns to leave out and which exons to keep and bind together. Once the
introns are cleaved and removed, the exons are joined together by
aphosphodiester bond.
Regulatory Proteins-
As noted above, splicing is regulated by repressor proteins and activator
important are the silencers and enhancers that are found on the messenger
RNAs, also known as cis-acting sites. These regulatory functions work together
factors.
tRNA (tRNAi) containing the first amino acid of the finalpolypeptide chain all
to begin. First, the small ribosomal subunit binds to the tRNAi which carries
charged.) Next, the small ribosomal subunit with the charged tRNAi still
bound scans along the mRNA strand until it reaches the start codon AUG,
which indicates where translation will begin. The start codon also establishes
the reading frame for the mRNA strand, which is crucial to synthesizing the
mistranslation of the mRNA. The anticodon on the tRNAi then binds to the
and the small ribosomal subunit attaches to the large ribosomal subunit,
by the help of proteins called initiation factors which bind to the small
ribosomal subunit during initiation and are found in all three domains of life.
In addition, the cell spends GTP energy to help form the initiation complex.
site of the ribosome and the empty A site is ready for the next aminoacyl-
tRNA. The polypeptide synthesis begins and always proceeds from the N-
binds to the small 40S ribosomal subunit. Next, the initiatior tRNA charged
complex, and once all these components are bound to each other, they are
Eukaryotic initiation factors eIF1, eIF3, eIF4, and eIF5 help bring the 43S
mRNA's 5' m7G cap, the 43S complex starts travelling down the mRNA until it
reaches the initiation AUG codon at the start of the mRNA's reading frame.
Sequences around the AUG may help ensure the correct AUG is used as the
Once the 43S complex is at the initiation AUG, the tRNAi-Met is positioned
over the AUG. The anticodon on tRNAi-Met basepairs with the AUG codon. At
this point, the GTP bound to eIF2 in the 43S complexx is hydrolyzed to GDP
+ phosphate, and energy is released. This energy is used to release the eIF2
(with GDP bound to it) from the 43S complex, leaving the 40S ribosomal
subunit and the tRNAi-Met at the translation start site of the mRNA.
Next, eIF5 with GTP bound binds to the 40S ribosomal subunit complexed to
the mRNA and the tRNAi-Met. The eIF5-GTP allows the 60S large ribosomal
subunit to bind. Once the 60S ribosomal subunit arrives, eIF5 hydrolyzes its
bound GTP to GDP + phosphate, and energy is released. This energy powers
assembly of the two ribosomal subunits into the intact 80S ribosome, with
tRNAi-Met in its P site while also basepaired to the initiation AUG codon on
change and cannot bind to GTP. Therefore, the 43S complex cannot form
it binds the 40S ribosomal subunit and actively translates the protein .
The ability to fully assemble the ribosome directly affects the rate at which
Symmetric division maintains stem cell lines and asymmetric division yields
differentiated cells.
that can differentiate into specialized cells (asymmetric division) or can divide
to produce more stem cells (symmetric division). In mammals, there are two
broad types of stem cells: embryonic stem cells, which are isolated from
theinner cell mass of blastocysts, and adult stem cells, which are found in
various tissues. In adult organisms, stem cells and progenitor cells act as a
embryo, stem cells can differentiate into all of the specialized cells
(including ectoderm, endoderm and mesoderm cells) but also maintain the
stem cells.
There are three accessible sources of autologous adult stem cells in humans: (1)
bone marrow, which requires extraction by harvesting (i.e., drilling into bone);
(2) adipose tissue (lipid cells), which requires extraction by liposuction; and
drawn from the donor, passed through a machine that extracts the stem cells,
and returned to the donor). Stem cells can also be taken from umbilical cord
blood just after birth. Of all the stem cell types, autologous harvesting involves
the least risk. By definition, autologous cells are obtained from one's own
body, just as one may bank his or her own blood for elective surgical
procedures. Highly plastic adult stem cells are routinely used in medical
therapies, for example in bone marrow transplantation. Stem cells can now be
Embryonic cell lines and autologous embryonic stem cells generated through
future therapies.
on the other hand, produces only one stem cell and a progenitor cell with
when they leave that niche or no longer receive those signals. An asymmetric
cell division produces two daughter cells with different cellular fates. This is in
contrast to normal symmetric cell divisions, which give rise to daughter cells
two distinct daughter cells: one copy of the original stem cell as well as a
conferred on the daughters of a dividing cell. In one, the daughter cells are
from surrounding cells, or from the precursor cell. This mechanism is known
with neighboring cells and the micro and macro environment of the precursor
cell.In the second mechanism, the prospective daughter cells are inherently
different at the time of division of the mother cell. Because this latter
mechanism does not depend on interactions of cells with each other or with
distributed into each daughter cell. Animals are made up of a vast number of
distinct cell types. During development, the zygote undergoes many cell
divisions that give rise to various cell types, including embryonic stem cells.
Asymmetric divisions of these embryonic cells gives rise to one cell of the
same potency (self-renewal), and another that may be of the same potency or
for the differentiation of a subset of daughter cells while maintaining stem cell
Cellular Differentiation--
To develop a multicellular organisms, cells must differentiate to specialize for
body: germ cells, somatic cells, and stem cells. Each of the approximately 100
trillion cells in an adult human has its own copy or copies of the genome except
certain cell types, such as red blood cells, that lack nuclei in their fully
differentiated state. Most cells are diploid; they have two copies of
varying proteomes between cell types . The variation in proteomes between cell
types is what drives differentiation and thus, specialization of cells. The ability
Somatic cells are diploid cells that make up most of the human body, such as
the skin and muscle. Germ cells are any line of cells that give rise to gametes
eggs and spermand thus are continuous through the generations. Stem cells,
on the other hand, have the ability to divide for indefinite periods and to give
rise to specialized cells. They are best described in the context of normal
human development.
Embryonic Development
Development begins when a sperm fertilizes an egg and creates a single cell
that has the potential to form an entire organism. In the first hours
approximately four days after fertilization and after several cycles of cell
division, these cells begin to specialize, forming a hollow sphere of cells, called
a blastocyst. The blastocyst has an outer layer of cells, and inside this hollow
sphere, there is a cluster of cells called the inner cell mass. The cells of the
inner cell mass go on to form virtually all of the tissues of the human body.
Although the cells of the inner cell mass can form virtually every type of cell
found in the human body, they cannot form an organism. These cells are
1. Hematopoietic stem cells (adult stem cells) from the bone marrow that give
2. Mesenchymal stem cells (adult stem cells) from the bone marrow that give rise
3. Epithelial stem cells (progenitor cells) that give rise to the various types of skin
cells
tissue
the most proximal, or interior). The ectoderm ends up forming the skin and
the nervous system, the mesoderm forms the bones and muscular tissue, and