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Submitted to: Dr. Aleena Samreen
Submitted by: Faiza Naeem
Roll:no: 14
M.phil
CAMB,PU
• Gene is a functional unit of genetic information coded
in the form of genetic code which deciphers to express
to generate the products that may be RNA or finally
protein.
• Genes are expressed through transcription and
translation.
• The expression of a gene (or a part of the genome) can
be regulated in many ways depending on cell
organization and needs of the organism.
• In all organisms, structural genes can be classified into two
groups
1. Constitutive genes, also called “housekeeping” genes :
encoding RNA and proteins having basal vital functions
such as rRNA, ribosomal proteins, proteins of cellular
respiratory system, … These genes are mostly expressed
continually and with a stable amount.
2. Inducible genes : encoding proteins necessary for the
survival of the organism in changing environment. These
genes must be rapidly “switch on” or “off” depending on
the temporary needs of the organism for their products.
Gene expression is a series of events or stages at different level
up to release of protein via mRNA. The major level of that is
transcription which is synthesis of mRNA and translation
leading to the synthesis of protein, a functional molecule of
genes.
Gene regulation is a series of events or stages in which their
must be controlled production of the gene product i.e., of RNA
and protein by the cell. Another word the controlled expression
of gene is called gene regulation. The control must be at various
steps in broad sense at transcription level or at translation level.
 Constitutive vs. regulated gene expression.
 Gene regulation can be achieved at several levels
along polypeptide synthesis (different in prokaryotes
and eukaryotes).
 Transcription proceeds through a series of defined
processes : initiation, elongation and termination.
 Transcription initiation is regulated by trans-acting
proteins (activators o repressors) that bind to cis-
acting Sites in or near promoters.
 Activation or repression by activators or repressors
can be regulated by co-‐regulators (small molecules in
prokaryotes)
The two well studied main mechanisms of transcriptional control of
gene expression are
• The operons : Genes involved in a metabolic pathway are
regrouped into a gene cluster controlled by common regulatory
sequences and proteins. The expression of these genes are then
rapid and synchronized.
• The cascades of gene expression : Under some environmental
conditions, expression of a first set of genes can be “switch on”,
and one or more of the products of this first gene set will “switch
on” a second gene set. This event could be repeated many times to
mobilize wider gene sets to achieve a special metabolic pathway.
• Gene expression in bacteria is controlled by the operon
model.
• A cluster of functionally related genes can be under
coordinated control by a single on off “switch”.
• The regulatory “switch” is a segment of DNA called an
operator usually positioned within the promoter.
• An operon is the entire stretch of DNA that includes the
operator, the promoter, and the genes that they control.
• - The operon can be switched off by a protein repressor
which prevents gene transcription by binding to the
operator and blocking RNA polymerase.
• The repressor is the product of a separate
regulatory gene.
• The repressor can be in an active or
inactive form, depending on the presence
of other molecules.
• A co-repressor is a molecule that
cooperates with a repressor protein to
switch an operon off.
Negative regulation Positive regulation
• The lac, or lactose, operon is found in E. coli and some other
enteric bacteria. This operon contains genes coding for proteins in
charge of transporting lactose into the cytosol and digesting it into
glucose. This glucose is then used to make energy.
• TURNING “ON” OF LAC OPERON
• E. coli bacteria can break down lactose, but it's not their favorite
fuel. If glucose is around, they would much rather use that.
Glucose requires fewer steps and less energy to break down than
lactose. However, if lactose is the only sugar available, the E. coli
will go right ahead and use it as an energy source.
• To use lactose, the bacteria must express the lac operon genes,
which encode key enzymes for lactose uptake and metabolism.
CONDITIONS
• Lactose is available, and
• Glucose is not available
REGULATORY PROTEINS
• One, the lac repressor, acts as a lactose sensor.
• The other, catabolite activator protein (CAP), acts as a
glucose sensor.
These proteins bind to the DNA of the lac operon and
regulate its transcription based on lactose and glucose
levels. Let's take a look at how this works.
• Unlike bacterial cells and most single cell eukaryotes,
cells in multicellular organisms have relatively few
genes that are directly and reversibly regulated by
environmental conditions.
• Instead multicellular organisms have many different,
specialized cells. Hence, tissue--‐specific gene control
is important for development and differentiation.
• Every gene has more than one gene regulator (all of
which must be on for the gene to function).
• Eukaryotic regulatory elements are usually several Kb
away from the promoter.
• Eukaryotic gene expression involves many steps, and almost all
of them can be regulated. Different genes are regulated at
different points, and it’s not uncommon for a gene (particularly
an important or powerful one) to be regulated at multiple steps.
 Genome Level (Chromatin Remodeling and DNA
rearrangements)
Transcriptional Control
Post-Transcriptional Control
Translational Control
Post-Tranla5onal Control (protein activity control)
Genes within highly packed heterochromatin are usually not
expressed. Chemical modifications to histones and DNA of
chromatin influence both chromatin structure and gene expression.
Histone Modifications
• In histone acetylation, acetyl groups are attached to positively
charged lysine in histone tails.
• This process loosens chromatin structure, thereby promoting the
initiation of transcription.
• The addition of methyl groups (methylation) can condense
chromatin; the addition of phosphate groups (phosphorylation)
next to a methylated amino acid can loosen chromatin.
DNA Methylation
• DNA methylation, the addition of methyl groups to certain bases in
DNA, is associated with reduced transcription in some species.
• DNA methylation can cause long-term inactivation of genes in cellular
differentiation.
• In genomic imprinting, methylation regulates expression of either the
maternal or paternal alleles of certain genes at the start of development.
Epigenetic Inheritance
• Although the chromatin modifications just discussed do not alter DNA
sequence, they may be passed to future generations of cells.
• The inheritance of traits transmitted by mechanisms not directly
involving the
• nucleotide sequence is called epigenetic inheritance.
For many genes, transcription is the key on/off control point:
• If a gene is not transcribed in a cell, it can't be used to make a
protein in that cell.
• If a gene does get transcribed, it is likely going to be used to
make a protein (expressed). In general, the more a gene is
transcribed, the more protein that will be made.
• Proteins called transcription factors, however, play a
particularly central role in regulating transcription. These
important proteins help determine which genes are active in
each cell of your body.
Some transcription factors activate transcription. For instance,
they may help the general transcription factors and/or RNA
polymerase bind to the promoter, as shown in the diagram below.
Other transcription factors repress transcription. This repression
can work in a variety of ways. As one example, a repressor may
get in the way of the basal transcription factors or RNA
polymerase, making it so they can't bind to the promoter or begin
transcription.
The binding sites for transcription factors are often close to a
gene's promoter. However, they can also be found in other parts
of the DNA, sometimes very far away from the promoter, and
still affect transcription of the gene.
Alternative splicing
In the process of alternative splicing, different portions of an
mRNA can be selected for use as exons. This allows either of two
(or more) mRNA molecules to be made from one pre-mRNA.
• Small regulatory RNAs
A recently discovered class of regulators, called small
regulatory RNAs, can control mRNA lifespan and translation
microRNA
The miRNA directs the protein complex to "matching" mRNA
molecules (ones that form base pairs with the miRNA). When
the RNA-protein complex binds
• If the miRNA and its target match perfectly, an enzyme in the
RNA-protein complex will typically chop the mRNA in half,
leading to its breakdown.
• If the miRNA and its target have some mismatches, the RNA-
protein complex may instead bind to the mRNA and keep it
from being translated.
These are not the only ways that miRNAs inhibit expression of
their targets, and scientists are still investigating their many
modes of action
• In order for translation to begin, the ribosome, an RNA-and-
protein complex that houses translation, must assemble on the
mRNA. This process involves many “helper” proteins, which
make sure the ribosome is correctly positioned. Translation can
be regulated globally (for every mRNA in the cell) through
changes in the availability or activity of the “helper” proteins.
• There are also regulatory mechanisms that act on proteins
that have already been made. In these cases, an "edit" to
the protein – such as removal of amino acids, or addition
of a chemical modification – can lead to a change in its
activity or behavior. These processing and modification
steps can be targets for regulation.
• Addition or removal of chemical groups may regulate
protein activity or the length of time a protein remains in
the cell before it undergoes "recycling." Sometimes,
chemical modifications can also determine where a
protein is found in the cell—for example, in the nucleus
or cytoplasm, or attached to the plasma membrane.
• Phosphorylation
Ubiquitination
• http://faculty.muhs.edu/klestinski/ap_bio_18_notes.pdf
• Gene: Expression and Regulation ARVIND KUMAR School of Biotechnology,
Banaras Hindu University, Varanasi–221 005, India
• http://csls-text.c.u-tokyo.ac.jp/pdf/Chap_04.pdf
• www.montefiore.ulg.ac.be/~kbessonov/.../Lecture%208_FD_GeneExpr_2015.pd
f
How Genes Are Controlled
PowerPoint® Lectures for Campbell Essential Biology, Fifth Edition, and Campbell
Essential Biology with Physiology,
Fourth Edition Eric J. Simon, Jean L. Dickey, and Jane B. Reece
https://www.khanacademy.org/science/biology/gene-regulation/gene-regulation-in-
eukaryotes/a/regulation-after-transcription
• https://www.khanacademy.org/science/biology/gene-regulation/gene-regulation-
in-bacteria/a/the-lac-operon
• https://courses.lumenlearning.com/wmopen-biology1/chapter/eukaryotic-gene-
regulation/

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Regulation of gene expression 1

  • 1. Submitted to: Dr. Aleena Samreen Submitted by: Faiza Naeem Roll:no: 14 M.phil CAMB,PU
  • 2. • Gene is a functional unit of genetic information coded in the form of genetic code which deciphers to express to generate the products that may be RNA or finally protein. • Genes are expressed through transcription and translation. • The expression of a gene (or a part of the genome) can be regulated in many ways depending on cell organization and needs of the organism.
  • 3.
  • 4. • In all organisms, structural genes can be classified into two groups 1. Constitutive genes, also called “housekeeping” genes : encoding RNA and proteins having basal vital functions such as rRNA, ribosomal proteins, proteins of cellular respiratory system, … These genes are mostly expressed continually and with a stable amount. 2. Inducible genes : encoding proteins necessary for the survival of the organism in changing environment. These genes must be rapidly “switch on” or “off” depending on the temporary needs of the organism for their products.
  • 5.
  • 6. Gene expression is a series of events or stages at different level up to release of protein via mRNA. The major level of that is transcription which is synthesis of mRNA and translation leading to the synthesis of protein, a functional molecule of genes. Gene regulation is a series of events or stages in which their must be controlled production of the gene product i.e., of RNA and protein by the cell. Another word the controlled expression of gene is called gene regulation. The control must be at various steps in broad sense at transcription level or at translation level.
  • 7.
  • 8.  Constitutive vs. regulated gene expression.  Gene regulation can be achieved at several levels along polypeptide synthesis (different in prokaryotes and eukaryotes).  Transcription proceeds through a series of defined processes : initiation, elongation and termination.  Transcription initiation is regulated by trans-acting proteins (activators o repressors) that bind to cis- acting Sites in or near promoters.  Activation or repression by activators or repressors can be regulated by co-‐regulators (small molecules in prokaryotes)
  • 9. The two well studied main mechanisms of transcriptional control of gene expression are • The operons : Genes involved in a metabolic pathway are regrouped into a gene cluster controlled by common regulatory sequences and proteins. The expression of these genes are then rapid and synchronized. • The cascades of gene expression : Under some environmental conditions, expression of a first set of genes can be “switch on”, and one or more of the products of this first gene set will “switch on” a second gene set. This event could be repeated many times to mobilize wider gene sets to achieve a special metabolic pathway.
  • 10. • Gene expression in bacteria is controlled by the operon model. • A cluster of functionally related genes can be under coordinated control by a single on off “switch”. • The regulatory “switch” is a segment of DNA called an operator usually positioned within the promoter. • An operon is the entire stretch of DNA that includes the operator, the promoter, and the genes that they control. • - The operon can be switched off by a protein repressor which prevents gene transcription by binding to the operator and blocking RNA polymerase.
  • 11. • The repressor is the product of a separate regulatory gene. • The repressor can be in an active or inactive form, depending on the presence of other molecules. • A co-repressor is a molecule that cooperates with a repressor protein to switch an operon off.
  • 13. • The lac, or lactose, operon is found in E. coli and some other enteric bacteria. This operon contains genes coding for proteins in charge of transporting lactose into the cytosol and digesting it into glucose. This glucose is then used to make energy. • TURNING “ON” OF LAC OPERON • E. coli bacteria can break down lactose, but it's not their favorite fuel. If glucose is around, they would much rather use that. Glucose requires fewer steps and less energy to break down than lactose. However, if lactose is the only sugar available, the E. coli will go right ahead and use it as an energy source. • To use lactose, the bacteria must express the lac operon genes, which encode key enzymes for lactose uptake and metabolism.
  • 14. CONDITIONS • Lactose is available, and • Glucose is not available REGULATORY PROTEINS • One, the lac repressor, acts as a lactose sensor. • The other, catabolite activator protein (CAP), acts as a glucose sensor. These proteins bind to the DNA of the lac operon and regulate its transcription based on lactose and glucose levels. Let's take a look at how this works.
  • 15.
  • 16.
  • 17.
  • 18. • Unlike bacterial cells and most single cell eukaryotes, cells in multicellular organisms have relatively few genes that are directly and reversibly regulated by environmental conditions. • Instead multicellular organisms have many different, specialized cells. Hence, tissue--‐specific gene control is important for development and differentiation. • Every gene has more than one gene regulator (all of which must be on for the gene to function).
  • 19. • Eukaryotic regulatory elements are usually several Kb away from the promoter.
  • 20. • Eukaryotic gene expression involves many steps, and almost all of them can be regulated. Different genes are regulated at different points, and it’s not uncommon for a gene (particularly an important or powerful one) to be regulated at multiple steps.  Genome Level (Chromatin Remodeling and DNA rearrangements) Transcriptional Control Post-Transcriptional Control Translational Control Post-Tranla5onal Control (protein activity control)
  • 21.
  • 22. Genes within highly packed heterochromatin are usually not expressed. Chemical modifications to histones and DNA of chromatin influence both chromatin structure and gene expression. Histone Modifications • In histone acetylation, acetyl groups are attached to positively charged lysine in histone tails. • This process loosens chromatin structure, thereby promoting the initiation of transcription. • The addition of methyl groups (methylation) can condense chromatin; the addition of phosphate groups (phosphorylation) next to a methylated amino acid can loosen chromatin.
  • 23. DNA Methylation • DNA methylation, the addition of methyl groups to certain bases in DNA, is associated with reduced transcription in some species. • DNA methylation can cause long-term inactivation of genes in cellular differentiation. • In genomic imprinting, methylation regulates expression of either the maternal or paternal alleles of certain genes at the start of development. Epigenetic Inheritance • Although the chromatin modifications just discussed do not alter DNA sequence, they may be passed to future generations of cells. • The inheritance of traits transmitted by mechanisms not directly involving the • nucleotide sequence is called epigenetic inheritance.
  • 24.
  • 25. For many genes, transcription is the key on/off control point: • If a gene is not transcribed in a cell, it can't be used to make a protein in that cell. • If a gene does get transcribed, it is likely going to be used to make a protein (expressed). In general, the more a gene is transcribed, the more protein that will be made. • Proteins called transcription factors, however, play a particularly central role in regulating transcription. These important proteins help determine which genes are active in each cell of your body.
  • 26.
  • 27. Some transcription factors activate transcription. For instance, they may help the general transcription factors and/or RNA polymerase bind to the promoter, as shown in the diagram below.
  • 28. Other transcription factors repress transcription. This repression can work in a variety of ways. As one example, a repressor may get in the way of the basal transcription factors or RNA polymerase, making it so they can't bind to the promoter or begin transcription.
  • 29. The binding sites for transcription factors are often close to a gene's promoter. However, they can also be found in other parts of the DNA, sometimes very far away from the promoter, and still affect transcription of the gene.
  • 30.
  • 31. Alternative splicing In the process of alternative splicing, different portions of an mRNA can be selected for use as exons. This allows either of two (or more) mRNA molecules to be made from one pre-mRNA.
  • 32. • Small regulatory RNAs A recently discovered class of regulators, called small regulatory RNAs, can control mRNA lifespan and translation microRNA The miRNA directs the protein complex to "matching" mRNA molecules (ones that form base pairs with the miRNA). When the RNA-protein complex binds • If the miRNA and its target match perfectly, an enzyme in the RNA-protein complex will typically chop the mRNA in half, leading to its breakdown. • If the miRNA and its target have some mismatches, the RNA- protein complex may instead bind to the mRNA and keep it from being translated. These are not the only ways that miRNAs inhibit expression of their targets, and scientists are still investigating their many modes of action
  • 33.
  • 34. • In order for translation to begin, the ribosome, an RNA-and- protein complex that houses translation, must assemble on the mRNA. This process involves many “helper” proteins, which make sure the ribosome is correctly positioned. Translation can be regulated globally (for every mRNA in the cell) through changes in the availability or activity of the “helper” proteins.
  • 35. • There are also regulatory mechanisms that act on proteins that have already been made. In these cases, an "edit" to the protein – such as removal of amino acids, or addition of a chemical modification – can lead to a change in its activity or behavior. These processing and modification steps can be targets for regulation. • Addition or removal of chemical groups may regulate protein activity or the length of time a protein remains in the cell before it undergoes "recycling." Sometimes, chemical modifications can also determine where a protein is found in the cell—for example, in the nucleus or cytoplasm, or attached to the plasma membrane.
  • 37. • http://faculty.muhs.edu/klestinski/ap_bio_18_notes.pdf • Gene: Expression and Regulation ARVIND KUMAR School of Biotechnology, Banaras Hindu University, Varanasi–221 005, India • http://csls-text.c.u-tokyo.ac.jp/pdf/Chap_04.pdf • www.montefiore.ulg.ac.be/~kbessonov/.../Lecture%208_FD_GeneExpr_2015.pd f How Genes Are Controlled PowerPoint® Lectures for Campbell Essential Biology, Fifth Edition, and Campbell Essential Biology with Physiology, Fourth Edition Eric J. Simon, Jean L. Dickey, and Jane B. Reece https://www.khanacademy.org/science/biology/gene-regulation/gene-regulation-in- eukaryotes/a/regulation-after-transcription • https://www.khanacademy.org/science/biology/gene-regulation/gene-regulation- in-bacteria/a/the-lac-operon • https://courses.lumenlearning.com/wmopen-biology1/chapter/eukaryotic-gene- regulation/