Regulation of Gene Expression

3/17/24
Regulation of gene expression

BCH2201
Barbara Nerima (PhD)
Introduction
v What is gene expression?
vIf one expressed an organism`s entire genome, you cannot

get the organism
vAlthough almost all cells contain the same genetic information;

not all genes are expressed at the same time/rate/place
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Introduction
v Proteins may be needed at different times, in different
places and in different quantities
v Not all proteins are processed the same way;

phosphorylation, glycosylation, ubiquitination, nitrosylation,
methylation, acetylation, lipidation and proteolysis
v All these depend on the function of the protein
v What is control/regulation of gene expression?
v A wide range of mechanisms that are used by cells to

increase or decrease or stop, the production of specific
gene products (protein or RNA)
Introduction: Prokaryote vs eukaryote
vLack of nuclear membrane in prokaryotes; DNA is found in cytoplasm-

all processes take place simultaneously
vControl is mainly at Transcription level
vEukaryotes have nuclear membrane- control at many levels since

transcription & Translation are not coupled
https://courses.lumenlearning.com/wm-biology1/chapter/reading-prokaryotic-and-eukaryotic-
gene-regulation/
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Introduction: Prokaryote vs eukaryote

v Prokaryote gene expression typically is regulated by an
operon; the collection of controlling sites adjacent to
polycistronic protein-coding sequences
v Eukaryotic genes also are regulated in units of protein-

coding sequences and adjacent controlling sites, but
operons are not known to occur
v Short term: genes are quickly turned on or off in response to

the environment and daily demands of the cell
ü This occurs in both eukaryotes and prokaryotes
v Long term: gene regulation in development/differentiation

ü Occurs in eukaryotes
Why regulation
v Regulated expression of genes is required for
Ø 1. Adaptation: Organisms adapt to environmental changes
by altering gene expression
a) Bacteria are highly versatile and responsive organisms:

the rate of synthesis of some proteins in bacteria may
vary more than a 1000-fold in response to the supply of
nutrients or to environmental challenges
b) Cells of multicellular organisms in general evolved the

ability to maintain a stable environment (homeostasis)
-However they also respond to varying conditions e.g hormones and
growth factors, disease
-change shape, growth rate, and other characteristics, disease
cure/pathology
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Why regulation
Ø 2. Differentiation and development
Tissue-specific differentiation and development
ü The genetic information present in each somatic cell of a
metazoan organism is practically identical
ü The exceptions in the genetic information are found in those

few cells that have amplified or rearranged genes in order to
perform specialized cellular functions e.g turn off certain genes
E.g 1. Cells from muscle and nerve

2. the β cells of the pancreas make the protein hormone insulin, while the α
cells of the pancreas make the hormone glucagon
3. the lymphocytes of the immune system are the only cells in the body that
make antibodies,
4. developing red blood cells are the only cells that make the oxygen-transport
protein hemoglobin
These diverse properties are the result of differentiation and differences in gene
expression
Why regulation
v Expression of genetic information is regulated during ontogeny
and differentiation of the organism and its cellular components
v Cell differentiation: where a cell changes from one cell type to

another (specialized); no change in DNA sequences
v Cell differentiation occurs numerous times during the

development of a multicellular organism
v Differentiation can result in changes in cell size, shape,

membrane potential, metabolic activity, responsiveness to signals
v Some genes are turned on and off depending on stages
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Types of gene regulation

v Positive regulation
ü Expression of genetic information is quantitatively
increased by the presence of a specific regulatory element
ü The element or molecule mediating positive regulation is

a positive regulator/Enhancer/Activator
v Negative regulation
üExpression of genetic information is reduced by the
presence of a specific regulatory element
üThe element or molecule mediating negative regulation is

said to be a negative regulator/Silencer/Repressor
Types of gene regulation

v Double negative regulation
ü Double negative regulation has the effect of acting as a
positive regulation
ü An effector that inhibits the function of a negative regulator

will bring about a positive regulation; allolactose binds to
repressor
v Autoregulation
ü A protein regulates its own transcription ie Feedback loops
v RNA-binding proteins (RBPs) are key regulators in post-
transcriptional control of gene expression
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Types of responses to gene regulation
Type A responses
v Type A response- an increased extent of gene
expression dependent upon the continued presence of the
inducing signal
v When the inducing signal is removed, amount of gene

expression diminishes to its basal level
v The amount repeatedly increases in response to the

reappearance of the specific signal
v Common in prokaryotes in response to signals in

response to intracellular changes in nutrients. In
eukaryotes, response to hormones, growth factors,
nutrients
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Type A responses
Type B responses
v Type B response exhibits an increased amount of gene
expression that is transient even in the continued
presence of the regulatory signal
v After the regulatory signal has terminated and the cell has
been allowed to recover, a second transient response to a
subsequent regulatory signal may be observed
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Type C Responses
v The type C response pattern exhibits, in response to the
regulatory signal an increased extent of gene expression
that persists indefinitely even after termination of the
signal
v The signal acts as a trigger in this pattern. Response

independent of initial signal
Type C Response
v Once expression of the gene is initiated in the cell, it
cannot be terminated even in the daughter cells
v It is therefore an irreversible and inherited alteration
v This type of response typically occurs during the

development of differentiated function in a tissue or organ
v beta and alpha, cells of the pancreas, muscle cells, etc.
lymphocytes
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Types of genes in Gene Expression

v Constitutive gene (House keeping genes)- one which is
expressed at a reasonably constant rate and are not known
to be subjected to regulation e.g enzymes of glycolytic
pathways, ribosomal genes
v They are required to maintain basic cellular function
v Are expressed in all cells under normal & patho-

physiological conditions, irrespective of tissue type,
developmental stage, Cell cycle state, external signal
v Constitutive genes represent the minimum set of genes

required to maintain life
https://www.genomics-online.com/resources/16/5049/housekeeping-genes/

v They have been used as internal controls for experimental
studies e.g if you would like to compare gene expression
between an HIV-infected and Uninfected person
v Therefore used for normalization of data; same quantities of

RNA should have the same expression levels of these
genes
v Constitutive mutation-mutation resulting in constitutive

expression of what was formerly a regulated gene: lead to
some forms of cancer
https://www.genomics-online.com/resources/16/5049/housekeeping-genes/
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v Facultative gene/inducible gene: expressed only when
needed; their expression is regulated
v One whose expression increases in response to an inducer

or activator e.g
-Alkaline phosphatase gene: induced by bile or Vitamin A
-the glucose transporter proteins that muscle cells produce in
response to insulin are the product of inducible genes. Insulin
stimulates their activity
v Its expression is either responsive to environmental change

or dependent on the position in the cell cycle
LOUISE CHANG, et al 2004

v Inducible genes can be activated by compounds structurally
similar to their substrates e.g IPTG (lactose analog) in
experiments (β-galactosidase)
v Inducible genes have relatively low basal rates of transcription
v Silenced (Repressed) genes are those that have been

permanently turned off. E.g some genes needed for nerve cell
function will be silenced in muscle cells. Gene silencing is part of
the process of cells acquiring their different identities/cell fate
v Gene silencing is the regulation of gene expression in a cell to

prevent the expression of a certain gene e.g genes on one of the
X chromosomes in females are silenced during embryonic
development
Ahmed et al 2021
10

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3/17/24

vIf one expressed an organism`s entire genome, you cannot

vAlthough almost all cells contain the same genetic information;

v Not all proteins are processed the same way;

v All these depend on the function of the protein

v What is control/regulation of gene expression?

v A wide range of mechanisms that are used by cells to

Introduction: Prokaryote vs eukaryote

vLack of nuclear membrane in prokaryotes; DNA is found in cytoplasm-

vControl is mainly at Transcription level

vEukaryotes have nuclear membrane- control at many levels since

Introduction: Prokaryote vs eukaryote

v Eukaryotic genes also are regulated in units of protein-

v Short term: genes are quickly turned on or off in response to

v Long term: gene regulation in development/differentiation

a) Bacteria are highly versatile and responsive organisms:

b) Cells of multicellular organisms in general evolved the

ü The exceptions in the genetic information are found in those

E.g 1. Cells from muscle and nerve

v Cell differentiation: where a cell changes from one cell type to

v Cell differentiation occurs numerous times during the

v Differentiation can result in changes in cell size, shape,

v Some genes are turned on and off depending on stages

Types of gene regulation

ü The element or molecule mediating positive regulation is

üThe element or molecule mediating negative regulation is

Types of gene regulation

ü An effector that inhibits the function of a negative regulator

Types of responses to gene regulation

v When the inducing signal is removed, amount of gene

v The amount repeatedly increases in response to the

v Common in prokaryotes in response to signals in

v The signal acts as a trigger in this pattern. Response

v It is therefore an irreversible and inherited alteration

v This type of response typically occurs during the

Types of genes in Gene Expression

v They are required to maintain basic cellular function

v Are expressed in all cells under normal & patho-

v Constitutive genes represent the minimum set of genes

Types of genes in Gene Expression

v Therefore used for normalization of data; same quantities of

v Constitutive mutation-mutation resulting in constitutive

Types of genes in Gene Expression

v One whose expression increases in response to an inducer

v Its expression is either responsive to environmental change

LOUISE CHANG, et al 2004

Types of genes in Gene Expression

v Inducible genes have relatively low basal rates of transcription

v Silenced (Repressed) genes are those that have been

v Gene silencing is the regulation of gene expression in a cell to

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