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Regulation of gene expression

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M
MANSI

CONCEPT ON GENE EXPRESSION, GENE THEORY, STAGES IN PROKARYOTES AND EUKARYOTES, TRANSCRIPTION AND TRANSLATION...

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MANSI YADAV SECTION-C ROLL NO.-204 MEDICAL SC. FIRST YEAR.. REGULATION OF GENE EXPRESSION…
MODERN CONCEPT OF GENES… A gene may be defined as a segment of DNA which is responsible for inheritance and expression of a particular character. It provides instructions for the synthesis of a specific protein or RNA. They are the functional unit of hereditary, variation, mutation and evolution… Modern Concept of Gene Seymour Benzer in 1955 introduced the 3 terms-: 1) CISTRON { Unit of FUNCTION }  Segment of DNA having information of synthesis of particular protein or RNA.  Responsible for expression of a trait.  Can be several bp long. 2) MUTON { Unit of MUTATION }  Segment of DNA that undergoes mutation  Consists of few nucleotides (1 or few bp) 3) RECON { Unit of RECOMBINATION }  Segment of DNA that participates in recombination through crossing over during meiosis  Consists of few to many bp
Objective :  What is Gene expression?  Necessity of regulation of gene expression  Different types of gene regulation  Gene regulation in prokaryotes Gene regulation in Eukaryotes A. Lac operon B. Tryptophan operon 1. At transcription level 2. At translation 3. Modification of DNA
∂ What is gene expression? Formation of gene products  RNA and Protein  Gene expression is the process by which the instructions in our DNA are converted into a functional product, such as a protein.  Normal growth , development and functioning of an organism  Production of gene product according to the requirement of the body ∂ Necessity of Gene Expression and regulation
Regulation of gene expression
Because it is the first stage of gene expression. Gene regulation at the first stage will be quick and will save a lot of energy in the organism that can be utilized by the cell for other useful purposes. QUESTION ? Why is transcription a particularly important level of gene regulation in both bacteria and eukaryotes? ANSWER -
Differences in the Regulation of Gene Expression of Prokaryotic and Eukaryotic Organisms Prokaryotic Organisms Eukaryotic Organisms Lack a membrane-bound nucleus. Contain nucleus. DNA is found in the cytoplasm. DNA is confined to the nuclear compartment. RNA transcription and protein formation occur almost simultaneously. RNA transcription occurs prior to protein formation, and it takes place in the nucleus. Translation of RNA to protein occurs in the cytoplasm. Gene expression is regulated at the transcriptional level. Gene expression is regulated at many levels (epigenetic, transcriptional, nuclear shuttling, post-transcriptional, translational, and post-translational).
Regulation of Gene Expression in Prokaryotes…
A. Constitutive gene expression - essential genes for living cells & housekeeping genes B. Inducible gene expression - enzymes in catabolic pathways C. Repressible gene expression - enzymes in anabolic pathways Type of genes expression A. Positive regulation---- Enhancer/Activator B. Negative regulation---- Repressor/ Silencer Regulation of gene expression In positive control, binding of activator protein triggers the transcription whereas in negative control, binding of repressor protein inhibits the transcription.
Bacterial gene organization Cluster of genes under the control of the same promoter and operator Promoter, operator & structural gene(s) In E.coli , 25 operons controlling 250 genes Inducible & Repressible operons Lac operon and Trp operon What is “Operon”? Model  Described by Jacob and Monod in 1961 .  Hypothesis: Based on the regulation of lactose metabolism by the intestinal bacterium E coli  Led to the discovery of basic principles of Gene transcription activation and Repression
An operon is made up of 4 basic DNA components: 1) Promoter – a nucleotide sequence that enables a gene to be transcribed. The promoter is recognized by RNA polymerase, which then initiates transcription. 2) Regulator – These genes control the operator gene in cooperation with certain compounds called inducers and corepressors present in the cytoplasm. 3) Operator – a segment of DNA that a repressor binds to. It is classically defined in the lac operon as a segment between the promoter and the genes of the operon. 4) Structural genes – the genes that are co- regulated by the operon. TypeS- I. Catabolic (inducible) such as Lac operon II. Anabolic (repressible) such as Trp operon Ligands which bind to the activators to “switch on” gene expression in positive control are called inducers ; those binding to the repressors and “switching off” gene expression are called co-repressors. Inducers and co- repressors are known as effectors….
Induction 1. It turns the operon on. 2. It starts transcription and translations. 3. It is caused by a new metabolite which needs enzymes to get metabolized. 4. It operates in a catabolic pathway. 5. Repressor is prevented by the inducer from joining the operator gene. Repression 1. It turns the operon off. 2. It stops transcription and translation. 3. It is caused by an excess of existing metabolite. 4. It operates in an anabolic pathway. 5. Apo repressor is enabled by a co- repressor to join the operator gene. TYPE OF OPERON PRESENCE OF METABOLITE EFFECT ON OPERON EXAMPLE INDUCIBLE LACTOSE ON Lac Operon REPRESSIBLE TRYPTOPHAN OFF Trp Operon
1. Regulator gene (Lac I) 2. Promoter 3. Operator 4. Structural genes a) Beta-galactosidase (lacZ) -- Breaks lactose into glucose + galactose. Converts lactose to the allolactose, regulates lac operon. b) Beta Galactoside permease (lacY) -- Transports lactose across cytoplasmic membrane. c) Thiogalactoside transacetylase (lacA) -- Trans- acetylation of lactose. *Catabolite gene activator protein (CAP) *Cyclic Adenosine Monophosphate (cAMP)  Two regulators turn the operon "on" and "off" in response to lactose and glucose levels: the lac repressor and CAP.  The lac repressor acts as a lactose sensor. It normally blocks transcription of the operon, but stops acting as a repressor when lactose is present. The lac repressor senses lactose indirectly, through its isomer allolactose.  CAP acts as a glucose sensor. It activates transcription of the operon, but only when glucose levels are low. CAP senses glucose indirectly, through the "hunger signal" molecule cAMP. The lac operon is considered an inducible operon because it is usually turned off (repressed), but can be turned on in the presence of the inducer allolactose.
INDUCER IS PRESENT INDUCER IS ABSENT The repressor of the operon is synthesized from the regulatory gene. The repressor protein binds to the operator region of the operon and prevents RNA polymerase from transcribing the operon. In the presence of an inducer, such as lactose or allolactose, the repressor is inactivated by interaction with the inducer. This allows RNA polymerase access to the promoter and transcription proceeds. *Regulation of lac operon by repressor is referred to as negative regulation…
POSITIVE CONTROL AND CATABOLITE REPRESSION 1. cAMP―adenosine-3′,5′-cyclic monophosphate 2. The concentration of cAMP is inversely proportional to the level of available glucose. • CAP is only active when glucose levels are low (cAMP levels are high). Thus, the lac operon can only be transcribed at high levels when glucose is absent. • This strategy ensures that bacteria only turn on the lac operon and start using lactose after they have used up all of the preferred energy source (glucose). a. The positive effect is activated by CAP. b. cAMP is bound to CAP, together CAP–cAMP complex binds to a site slightly upstream from the lac gene promoter.
Q-What is the meaning of this two-stages growing pattern ? A-In stage 1, bacteria grow using glucose as carbon source. When glucose is totally consumed, bacteria will stop growing (first plateau). After this lag phase, bacteria grow again (stage 2) using lactose until this second sugar is also finished (second plateau)…. Summary of Lac Operon Responses GLUCOSE LACTOSE CAP BINDS REPRESSOR LEVEL OF TRANSCRI PTION + - - + NO + + - - LOW- LEVEL - - + + NO - + + - HIGH- LEVEL
1. The trp operon, found in E. coli bacteria, is a group of genes that encode biosynthetic enzymes for the amino acid tryptophan needed for their survival by building proteins. 2. The trp operon is regulated by the trp repressor. When bound to tryptophan, the trp repressor blocks expression of the operon. 3. E. coli can also make their own tryptophan using enzymes that are encoded by 5 genes. These 5 genes are located next to each other in what is called the trp operon i.e. E,D,C,B,A.
The trp repressor does not always bind to DNA. Instead, it binds and blocks transcription only when tryptophan is present. When tryptophan is around, it attaches to the repressor molecules and changes their shape so they become active. A small molecule like tryptophan, which switches a repressor into its active state, is called a corepressor. When there is little tryptophan in the cell, on the other hand, the trp repressor is inactive (because no tryptophan is available to bind to and activate it). It does not attach to the DNA or block transcription, and this allows the trp operon to be transcribed by RNA polymerase. Trp ABSENT Trp PRESENT
Regulation of Gene Expression in Eukaryotes….
In eukaryotes like humans, gene expression involves many steps, and gene regulation can occur at any of these steps. However, many genes are regulated primarily at the level of transcription.  Chromatin accessibility. The structure of chromatin (DNA and its organizing proteins) can be regulated. More open or “relaxed” chromatin makes a gene more available for transcription.  Transcription. Transcription is a key regulatory point for many genes. Sets of transcription factor proteins bind to specific DNA sequences in or near a gene and promote or repress its transcription into an RNA.  RNA processing. Splicing, capping, and addition of a poly-A tail to an RNA molecule can be regulated, and so can exit from the nucleus. Different mRNAs may be made from the same pre-mRNA by alternative splicing.  RNA stability. The lifetime of an mRNA molecule in the cytosol affects how many proteins can be made from it. Small regulatory RNAs called miRNAs can bind to target mRNAs and cause them to be chopped up.  Translation. Translation of an mRNA may be increased or inhibited by regulators. For instance, miRNAs sometimes block translation of their target mRNAs (rather than causing them to be chopped up).  Protein activity. Proteins can undergo a variety of modifications, such as being chopped up or tagged with chemical groups. These modifications can be regulated and may affect the activity or behavior of the protein.
Regulation of gene expression
• At the chromatin structure level, genes can be silenced by changing the degree of compacting or by chemical modifications of the DNA. Genes can also be hyperactivated through amplification. Proteins participating in the changeset of chromatin structure are called nucleosome modifiers. • Epigenetic inheritance is a gene expression control relying on control of chromatin structure independent of any DNA sequence changes. Epigenetic inheritance is mainly based on histone modifications and DNA methylation. Epigenetic regulations include X- inactivation and parental imprinting which is crucial for normal embryonic development. Abnormal epigenetic inheritance can cause cancers and many genetic disorders. *Modification of Histone Proteins is an Example of Epigenetic Control…
Transcription Factors  Groups of transcription factor binding sites called enhancers and s ilencers can turn a gene on/off in specific parts of the body.  Transcription factors that are activators boost a gene's transcription. Repress ors decrease transcription.  It allow cells to perform logic operations and combine different sources of information to "decide" whether to express a gene.  They are proteins that help turn specific genes "on" or "off" by binding to nearby DNA. Transcriptional regulation is control of whether or not an mRNA is transcribed from a gene in a particular cell.
 Transcription involves RNA Polymerase II and transcription factors.  RNA polymerase II - attaches to the promoter (TATA box).  The purpose of the promoter is to bind transcription factors that control the initiation of transcription. Within the promoter region, just upstream of the transcriptional start site, resides the TATA box (a repeat of thymine and adenine dinucleotides).  Control elements – non coding sequences of DNA where the transcription factors attach. A. Enhancer – control element far from a gene or intron. B. Activator – bind to enhancers to turn on transcription of a gene C. Repressors – inhibit gene expression • Turn off transcription • Block activators from binding to enhancers Transcription factors + enhancer + activator + RNA Polymerase II = transcription initiation complex  Needed for transcription to begin
Distal control element Activators Enhancer Promoter Gene TATA box General transcription factors DNA-bending protein Group of Mediator proteins RNA Polymerase II RNA Polymerase II RNA synthesis Transcription Initiation complex Chromatin changes Transcription RNA processing mRNA degradation Translation Protein processing and degradation A DNA-bending protein brings the bound activators closer to the promoter. Other transcription factors, mediator proteins, and RNA polymerase are nearby. 2 Activator proteins bind to distal control elements grouped as an enhancer in the DNA. This enhancer has three binding sites. 1 The activators bind to certain general transcription factors and mediator proteins, helping them form an active transcription initiation complex on the promoter. 3
a) Alternative RNA splicing is a mechanism that allows different combinations of introns, and sometimes exons, to be removed from the primary transcript. This allows different protein products to be produced from one gene. It acts as a mechanism of gene regulation. b) Control of RNA Stability : Proteins, called RNA-binding proteins (RBPs) can bind to the regions of the RNA just upstream or downstream of the protein-coding region. These regions in the RNA that are not translated into protein are called the untranslated regions, or UTRs. The region just before the protein-coding region is called the 5′ UTR, whereas the region after the coding region is called the 3′ UTR. c) microRNAs, or miRNAs, can also bind to the RNA molecule. miRNAs are short (21–24 nucleotides) RNA molecules that are made in the nucleus. miRNAs bind to mRNA along with a ribonucleoprotein complex called the RNA-induced silencing complex (RISC). The RISC- miRNA complex rapidly degrades the target mRNA. Post-transcriptional regulation occurs after the mRNA is transcribed but before translation begins. This regulation can occur at the level of mRNA processing, transport from the nucleus to the cytoplasm, or binding to ribosomes. Alternative RNA splicing Control of RNA Stability
a. After an mRNA has been transported to the cytoplasm, it is translated into proteins. Control of this process is largely dependent on the mRNA molecule. b. Translation can also be regulated at the level of binding of the mRNA to the ribosome. Once the mRNA bound to the ribosome, the speed and level of translation can still be controlled. c. An example of translational control occurs in proteins that are destined to end up in an organelle called the endoplasmic reticulum (ER). d. The first few amino acids of these proteins are a tag called a signal sequence. As soon as these amino acids are translated, a signal recognition particle (SRP) binds to the signal sequence and stops translation while the mRNA-ribosome complex is shuttled to the ER. Once they arrive, the SRP is removed and translation resumes. Translational Control
 The final level of control of gene expression in eukaryotes is post-translational regulation. This type of control involves modifying the protein after it is made to affect its activity.  When an enzyme is no longer needed, it is inhibited by a competitive or allosteric inhibitor, which prevents it from binding to its substrate. The inhibition is reversible, so that the enzyme can be reactivated later. This is more efficient than degrading the enzyme.  The activity or stability of proteins can also be regulated by adding functional groups, such as methyl, phosphate, or acetyl groups.  A phosphate group is attached to a protein. The effect of phosphorylation varies from protein to protein: some are activated by phosphorylation, while others are deactivated, and others yet simply change their behavior.
1. https://cnx.org/resources/0e5cca3cd82aa8ea1b9 6841daebcb1dae341e5a3/7- REGULATION%20OF%20GENE%20EXPRESSI ON%20IN%20EUKARYOTES.pdf 2. https://www.slideshare.net/MetheeSri/regulatio n-of-gene-expression-41008675 3. https://www.ncbi.nlm.nih.gov/pmc/articles/PM C3610329/ 4. https://rwu.pressbooks.pub/bio103/chapter/reg ulation-of-gene-expression/ 5. https://www.nature.com/scitable/topicpage/reg ulation-of-transcription-and-gene-expression-in- 1086/
Regulation of gene expression

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Regulation of gene expression

  • 1. MANSI YADAV SECTION-C ROLL NO.-204 MEDICAL SC. FIRST YEAR.. REGULATION OF GENE EXPRESSION…
  • 2. MODERN CONCEPT OF GENES… A gene may be defined as a segment of DNA which is responsible for inheritance and expression of a particular character. It provides instructions for the synthesis of a specific protein or RNA. They are the functional unit of hereditary, variation, mutation and evolution… Modern Concept of Gene Seymour Benzer in 1955 introduced the 3 terms-: 1) CISTRON { Unit of FUNCTION }  Segment of DNA having information of synthesis of particular protein or RNA.  Responsible for expression of a trait.  Can be several bp long. 2) MUTON { Unit of MUTATION }  Segment of DNA that undergoes mutation  Consists of few nucleotides (1 or few bp) 3) RECON { Unit of RECOMBINATION }  Segment of DNA that participates in recombination through crossing over during meiosis  Consists of few to many bp
  • 3. Objective :  What is Gene expression?  Necessity of regulation of gene expression  Different types of gene regulation  Gene regulation in prokaryotes Gene regulation in Eukaryotes A. Lac operon B. Tryptophan operon 1. At transcription level 2. At translation 3. Modification of DNA
  • 4. ∂ What is gene expression? Formation of gene products  RNA and Protein  Gene expression is the process by which the instructions in our DNA are converted into a functional product, such as a protein.  Normal growth , development and functioning of an organism  Production of gene product according to the requirement of the body ∂ Necessity of Gene Expression and regulation
  • 6. Because it is the first stage of gene expression. Gene regulation at the first stage will be quick and will save a lot of energy in the organism that can be utilized by the cell for other useful purposes. QUESTION ? Why is transcription a particularly important level of gene regulation in both bacteria and eukaryotes? ANSWER -
  • 7. Differences in the Regulation of Gene Expression of Prokaryotic and Eukaryotic Organisms Prokaryotic Organisms Eukaryotic Organisms Lack a membrane-bound nucleus. Contain nucleus. DNA is found in the cytoplasm. DNA is confined to the nuclear compartment. RNA transcription and protein formation occur almost simultaneously. RNA transcription occurs prior to protein formation, and it takes place in the nucleus. Translation of RNA to protein occurs in the cytoplasm. Gene expression is regulated at the transcriptional level. Gene expression is regulated at many levels (epigenetic, transcriptional, nuclear shuttling, post-transcriptional, translational, and post-translational).
  • 9. A. Constitutive gene expression - essential genes for living cells & housekeeping genes B. Inducible gene expression - enzymes in catabolic pathways C. Repressible gene expression - enzymes in anabolic pathways Type of genes expression A. Positive regulation---- Enhancer/Activator B. Negative regulation---- Repressor/ Silencer Regulation of gene expression In positive control, binding of activator protein triggers the transcription whereas in negative control, binding of repressor protein inhibits the transcription.
  • 10. Bacterial gene organization Cluster of genes under the control of the same promoter and operator Promoter, operator & structural gene(s) In E.coli , 25 operons controlling 250 genes Inducible & Repressible operons Lac operon and Trp operon What is “Operon”? Model  Described by Jacob and Monod in 1961 .  Hypothesis: Based on the regulation of lactose metabolism by the intestinal bacterium E coli  Led to the discovery of basic principles of Gene transcription activation and Repression
  • 11. An operon is made up of 4 basic DNA components: 1) Promoter – a nucleotide sequence that enables a gene to be transcribed. The promoter is recognized by RNA polymerase, which then initiates transcription. 2) Regulator – These genes control the operator gene in cooperation with certain compounds called inducers and corepressors present in the cytoplasm. 3) Operator – a segment of DNA that a repressor binds to. It is classically defined in the lac operon as a segment between the promoter and the genes of the operon. 4) Structural genes – the genes that are co- regulated by the operon. TypeS- I. Catabolic (inducible) such as Lac operon II. Anabolic (repressible) such as Trp operon Ligands which bind to the activators to “switch on” gene expression in positive control are called inducers ; those binding to the repressors and “switching off” gene expression are called co-repressors. Inducers and co- repressors are known as effectors….
  • 12. Induction 1. It turns the operon on. 2. It starts transcription and translations. 3. It is caused by a new metabolite which needs enzymes to get metabolized. 4. It operates in a catabolic pathway. 5. Repressor is prevented by the inducer from joining the operator gene. Repression 1. It turns the operon off. 2. It stops transcription and translation. 3. It is caused by an excess of existing metabolite. 4. It operates in an anabolic pathway. 5. Apo repressor is enabled by a co- repressor to join the operator gene. TYPE OF OPERON PRESENCE OF METABOLITE EFFECT ON OPERON EXAMPLE INDUCIBLE LACTOSE ON Lac Operon REPRESSIBLE TRYPTOPHAN OFF Trp Operon
  • 13. 1. Regulator gene (Lac I) 2. Promoter 3. Operator 4. Structural genes a) Beta-galactosidase (lacZ) -- Breaks lactose into glucose + galactose. Converts lactose to the allolactose, regulates lac operon. b) Beta Galactoside permease (lacY) -- Transports lactose across cytoplasmic membrane. c) Thiogalactoside transacetylase (lacA) -- Trans- acetylation of lactose. *Catabolite gene activator protein (CAP) *Cyclic Adenosine Monophosphate (cAMP)  Two regulators turn the operon "on" and "off" in response to lactose and glucose levels: the lac repressor and CAP.  The lac repressor acts as a lactose sensor. It normally blocks transcription of the operon, but stops acting as a repressor when lactose is present. The lac repressor senses lactose indirectly, through its isomer allolactose.  CAP acts as a glucose sensor. It activates transcription of the operon, but only when glucose levels are low. CAP senses glucose indirectly, through the "hunger signal" molecule cAMP. The lac operon is considered an inducible operon because it is usually turned off (repressed), but can be turned on in the presence of the inducer allolactose.
  • 14. INDUCER IS PRESENT INDUCER IS ABSENT The repressor of the operon is synthesized from the regulatory gene. The repressor protein binds to the operator region of the operon and prevents RNA polymerase from transcribing the operon. In the presence of an inducer, such as lactose or allolactose, the repressor is inactivated by interaction with the inducer. This allows RNA polymerase access to the promoter and transcription proceeds. *Regulation of lac operon by repressor is referred to as negative regulation…
  • 15. POSITIVE CONTROL AND CATABOLITE REPRESSION 1. cAMP―adenosine-3′,5′-cyclic monophosphate 2. The concentration of cAMP is inversely proportional to the level of available glucose. • CAP is only active when glucose levels are low (cAMP levels are high). Thus, the lac operon can only be transcribed at high levels when glucose is absent. • This strategy ensures that bacteria only turn on the lac operon and start using lactose after they have used up all of the preferred energy source (glucose). a. The positive effect is activated by CAP. b. cAMP is bound to CAP, together CAP–cAMP complex binds to a site slightly upstream from the lac gene promoter.
  • 16. Q-What is the meaning of this two-stages growing pattern ? A-In stage 1, bacteria grow using glucose as carbon source. When glucose is totally consumed, bacteria will stop growing (first plateau). After this lag phase, bacteria grow again (stage 2) using lactose until this second sugar is also finished (second plateau)…. Summary of Lac Operon Responses GLUCOSE LACTOSE CAP BINDS REPRESSOR LEVEL OF TRANSCRI PTION + - - + NO + + - - LOW- LEVEL - - + + NO - + + - HIGH- LEVEL
  • 17. 1. The trp operon, found in E. coli bacteria, is a group of genes that encode biosynthetic enzymes for the amino acid tryptophan needed for their survival by building proteins. 2. The trp operon is regulated by the trp repressor. When bound to tryptophan, the trp repressor blocks expression of the operon. 3. E. coli can also make their own tryptophan using enzymes that are encoded by 5 genes. These 5 genes are located next to each other in what is called the trp operon i.e. E,D,C,B,A.
  • 18. The trp repressor does not always bind to DNA. Instead, it binds and blocks transcription only when tryptophan is present. When tryptophan is around, it attaches to the repressor molecules and changes their shape so they become active. A small molecule like tryptophan, which switches a repressor into its active state, is called a corepressor. When there is little tryptophan in the cell, on the other hand, the trp repressor is inactive (because no tryptophan is available to bind to and activate it). It does not attach to the DNA or block transcription, and this allows the trp operon to be transcribed by RNA polymerase. Trp ABSENT Trp PRESENT
  • 20. In eukaryotes like humans, gene expression involves many steps, and gene regulation can occur at any of these steps. However, many genes are regulated primarily at the level of transcription.  Chromatin accessibility. The structure of chromatin (DNA and its organizing proteins) can be regulated. More open or “relaxed” chromatin makes a gene more available for transcription.  Transcription. Transcription is a key regulatory point for many genes. Sets of transcription factor proteins bind to specific DNA sequences in or near a gene and promote or repress its transcription into an RNA.  RNA processing. Splicing, capping, and addition of a poly-A tail to an RNA molecule can be regulated, and so can exit from the nucleus. Different mRNAs may be made from the same pre-mRNA by alternative splicing.  RNA stability. The lifetime of an mRNA molecule in the cytosol affects how many proteins can be made from it. Small regulatory RNAs called miRNAs can bind to target mRNAs and cause them to be chopped up.  Translation. Translation of an mRNA may be increased or inhibited by regulators. For instance, miRNAs sometimes block translation of their target mRNAs (rather than causing them to be chopped up).  Protein activity. Proteins can undergo a variety of modifications, such as being chopped up or tagged with chemical groups. These modifications can be regulated and may affect the activity or behavior of the protein.
  • 22. • At the chromatin structure level, genes can be silenced by changing the degree of compacting or by chemical modifications of the DNA. Genes can also be hyperactivated through amplification. Proteins participating in the changeset of chromatin structure are called nucleosome modifiers. • Epigenetic inheritance is a gene expression control relying on control of chromatin structure independent of any DNA sequence changes. Epigenetic inheritance is mainly based on histone modifications and DNA methylation. Epigenetic regulations include X- inactivation and parental imprinting which is crucial for normal embryonic development. Abnormal epigenetic inheritance can cause cancers and many genetic disorders. *Modification of Histone Proteins is an Example of Epigenetic Control…
  • 23. Transcription Factors  Groups of transcription factor binding sites called enhancers and s ilencers can turn a gene on/off in specific parts of the body.  Transcription factors that are activators boost a gene's transcription. Repress ors decrease transcription.  It allow cells to perform logic operations and combine different sources of information to "decide" whether to express a gene.  They are proteins that help turn specific genes "on" or "off" by binding to nearby DNA. Transcriptional regulation is control of whether or not an mRNA is transcribed from a gene in a particular cell.
  • 24.  Transcription involves RNA Polymerase II and transcription factors.  RNA polymerase II - attaches to the promoter (TATA box).  The purpose of the promoter is to bind transcription factors that control the initiation of transcription. Within the promoter region, just upstream of the transcriptional start site, resides the TATA box (a repeat of thymine and adenine dinucleotides).  Control elements – non coding sequences of DNA where the transcription factors attach. A. Enhancer – control element far from a gene or intron. B. Activator – bind to enhancers to turn on transcription of a gene C. Repressors – inhibit gene expression • Turn off transcription • Block activators from binding to enhancers Transcription factors + enhancer + activator + RNA Polymerase II = transcription initiation complex  Needed for transcription to begin
  • 25. Distal control element Activators Enhancer Promoter Gene TATA box General transcription factors DNA-bending protein Group of Mediator proteins RNA Polymerase II RNA Polymerase II RNA synthesis Transcription Initiation complex Chromatin changes Transcription RNA processing mRNA degradation Translation Protein processing and degradation A DNA-bending protein brings the bound activators closer to the promoter. Other transcription factors, mediator proteins, and RNA polymerase are nearby. 2 Activator proteins bind to distal control elements grouped as an enhancer in the DNA. This enhancer has three binding sites. 1 The activators bind to certain general transcription factors and mediator proteins, helping them form an active transcription initiation complex on the promoter. 3
  • 26. a) Alternative RNA splicing is a mechanism that allows different combinations of introns, and sometimes exons, to be removed from the primary transcript. This allows different protein products to be produced from one gene. It acts as a mechanism of gene regulation. b) Control of RNA Stability : Proteins, called RNA-binding proteins (RBPs) can bind to the regions of the RNA just upstream or downstream of the protein-coding region. These regions in the RNA that are not translated into protein are called the untranslated regions, or UTRs. The region just before the protein-coding region is called the 5′ UTR, whereas the region after the coding region is called the 3′ UTR. c) microRNAs, or miRNAs, can also bind to the RNA molecule. miRNAs are short (21–24 nucleotides) RNA molecules that are made in the nucleus. miRNAs bind to mRNA along with a ribonucleoprotein complex called the RNA-induced silencing complex (RISC). The RISC- miRNA complex rapidly degrades the target mRNA. Post-transcriptional regulation occurs after the mRNA is transcribed but before translation begins. This regulation can occur at the level of mRNA processing, transport from the nucleus to the cytoplasm, or binding to ribosomes. Alternative RNA splicing Control of RNA Stability
  • 27. a. After an mRNA has been transported to the cytoplasm, it is translated into proteins. Control of this process is largely dependent on the mRNA molecule. b. Translation can also be regulated at the level of binding of the mRNA to the ribosome. Once the mRNA bound to the ribosome, the speed and level of translation can still be controlled. c. An example of translational control occurs in proteins that are destined to end up in an organelle called the endoplasmic reticulum (ER). d. The first few amino acids of these proteins are a tag called a signal sequence. As soon as these amino acids are translated, a signal recognition particle (SRP) binds to the signal sequence and stops translation while the mRNA-ribosome complex is shuttled to the ER. Once they arrive, the SRP is removed and translation resumes. Translational Control
  • 28.  The final level of control of gene expression in eukaryotes is post-translational regulation. This type of control involves modifying the protein after it is made to affect its activity.  When an enzyme is no longer needed, it is inhibited by a competitive or allosteric inhibitor, which prevents it from binding to its substrate. The inhibition is reversible, so that the enzyme can be reactivated later. This is more efficient than degrading the enzyme.  The activity or stability of proteins can also be regulated by adding functional groups, such as methyl, phosphate, or acetyl groups.  A phosphate group is attached to a protein. The effect of phosphorylation varies from protein to protein: some are activated by phosphorylation, while others are deactivated, and others yet simply change their behavior.
  • 29. 1. https://cnx.org/resources/0e5cca3cd82aa8ea1b9 6841daebcb1dae341e5a3/7- REGULATION%20OF%20GENE%20EXPRESSI ON%20IN%20EUKARYOTES.pdf 2. https://www.slideshare.net/MetheeSri/regulatio n-of-gene-expression-41008675 3. https://www.ncbi.nlm.nih.gov/pmc/articles/PM C3610329/ 4. https://rwu.pressbooks.pub/bio103/chapter/reg ulation-of-gene-expression/ 5. https://www.nature.com/scitable/topicpage/reg ulation-of-transcription-and-gene-expression-in- 1086/