CH18: Regulation of Gene Expression

Define feedback inhibition

Define feedback inhibition

a cellular control mechanism that occurs when the end product of a biochemical pathway inhibits the enzyme that helped create it

Explain regulation of gene expression

refers to the mechanisms and processes that control the frequency, timing, and amount of gene product (RNA or protein) produced by a gene. This regulation can occur at various stages, including transcription, RNA processing, translation, and post-translational modifications, allowing cells to respond to internal and external stimuli.

Define operons

a cluster of genes under the control of a single promoter and regulatory elements, which are transcribed together as a single mRNA molecule. Operons are functional in prokaryotes and play a significant role in the regulation of gene expression.

What are the components of an operon?

1) Promoter: A DNA sequence where RNA polymerase binds to initiate transcription.

2) Operator: A regulatory region that controls the access of RNA polymerase to the promoter, often by being bound by a repressor protein.

3) Structural genes: Genes that are co-transcribed into a single mRNA molecule and encode proteins that usually have a related function.

4) Regulatory genes: Genes that produce repressors or activators that bind to the operator to regulate the transcription of the operon.

5) Enhancers: Additional regulatory sequences that can enhance the transcription process from a distance.

What is produced by an operon and how is an operon regulated?

a single messenger RNA (mRNA) molecule containing the code for multiple proteins, all of which are functionally related and transcribed together from a single promoter region on the DNA; the expression of these genes within an operon is regulated by a specific mechanism involving a repressor protein that binds to an operator site on the DNA, effectively turning gene expression on or off depending on environmental conditions.

Are operons present in prokaryotes? Are they present in eukaryotes?

produces a single mRNA molecule that encodes multiple related proteins. The regulation of an operon occurs through various means such as the binding of repressor proteins to the operator region, which blocks RNA polymerase from transcribing the structural genes when the corresponding substrate (e.g., an absence of lactose in the lac operon) is present. Conversely, when the substrate is present (e.g., lactose in the lac operon), it binds to the repressor protein, causing a conformational change that prevents the repressor from binding to the operator, allowing transcription to occur.

Define operator and explain its function

a segment of DNA located within an operon, acting as a regulatory switch. Its function is to control the transcription of certain genes by providing a binding site for repressor proteins. When a repressor protein binds to the operator, it blocks RNA polymerase from accessing the promoter region, thereby preventing transcription of the downstream structural genes. When the repressor is not bound, RNA polymerase can transcribe the operon, leading to the production of related proteins.

Define regulatory gene and explain its function

a gene that produces a product, usually a protein, which regulates the expression of other genes. Its function includes the production of molecules such as repressors or activators that bind to the operator regions within operons, influencing the transcription and expression of the structural genes. By modulating the activity of RNA polymerase, regulatory genes play a crucial role in controlling the timing and level of gene expression in response to various cellular signals and environmental conditions

Define repressor and explain how repressors affect gene expression

a type of protein that binds to the operator region of an operon, blocking RNA polymerase from transcribing the genes of the operon. When a repressor is bound to the operator, it prevents the transcription of structural genes, thereby inhibiting gene expression. Conversely, when certain molecules bind to the repressor, they can cause it to release from the operator, allowing RNA polymerase to transcribe the operon and leading to gene expression

Define corepressor and explain how corepressors work with repressors to regulate gene expression

a small molecule that cooperates with a repressor protein to inhibit gene expression. When a corepressor binds to a repressor protein, it causes a conformational change in the repressor, allowing it to bind to the operator region of an operon. This binding blocks RNA polymerase from accessing the promoter and prevents transcription of the structural genes within the operon. Corepressors play a critical role in the regulation of gene expression by facilitating the action of repressors in response to specific environmental signals or metabolic conditions.

Explain what the trp operon regulates and how the trp operon is regulated (hint: think about when tryptophan is needed and when it is not needed)

regulates the synthesis of the amino acid tryptophan in bacteria. It is a negative feedback system; when tryptophan levels are low, the operon is active, allowing the transcription of the genes required for tryptophan biosynthesis. Conversely, when tryptophan levels are high, it binds to the repressor protein, activating it and causing it to bind to the operator region of the operon. This binding prevents RNA polymerase from transcribing the genes needed for tryptophan production, effectively shutting down the operon.

Explain what the lac operon regulates and how the lac operon is regulated by lactose and glucose

The lac operon regulates the metabolism of lactose in bacteria. It is activated when lactose is present, causing the repressor to disengage from the operator, allowing transcription. High glucose levels inhibit the operon, while low glucose levels enhance its activation

Explain the role of general transcription factors

essential proteins that help facilitate the transcription of DNA into RNA by RNA polymerase. They bind to specific DNA sequences near the promoter region of a gene and assist in the assembly of the transcription machinery, ensuring that RNA polymerase can initiate transcription accurately and efficiently.

Define activator and explain how activators work

a type of protein that enhances gene expression by facilitating the binding of RNA polymerase to specific promoter regions of DNA.

work by binding to specific DNA sequences called enhancer regions, which can be located far from the promoter. Upon binding, they promote changes in the DNA structure that increase the likelihood of RNA polymerase engaging with the promoter, thereby enhancing the transcription of the corresponding gene

Define repressor and explain how repressors work

A protein that inhibits gene transcription by binding to the operator region of an operon.

Repressors block RNA polymerase from transcribing genes by binding to the operator, preventing access to the promoter. They can dissociate when certain molecules bind, allowing gene expression.

Define enhancer/distal control element

An enhancer is a regulatory DNA sequence that increases gene transcription by binding transcription factors. It can act at a distance from the gene, functioning independently of its position or orientation.

Define proximal control element

regulatory DNA sequence located close to the promoter of a gene that enhances transcription by providing binding sites for transcription factors. It plays a crucial role in the regulation of gene expression.

Explain how different proteins are expressed in the eye compared to the liver

Different proteins are expressed in the eye and liver due to distinct gene expression profiles influenced by tissue-specific transcription factors and regulatory elements. The eye requires proteins for visual function, such as opsins and crystallins, while the liver expresses proteins involved in metabolism, detoxification, and synthesis, such as albumin and cytochrome P450. This specificity in protein expression allows each organ to perform its unique physiological roles effectively

Explain what is meant by “transcription factories”

specialized structures within the cell nucleus where active transcription of multiple genes occurs simultaneously. These factories are enriched with RNA polymerase and transcription factors, allowing for efficient gene expression. They facilitate the coordination of transcription by bringing together genes that are being expressed and the necessary machinery for their transcription, thereby enhancing the overall efficiency of gene expression

Define pre RNA Are pre RNAs directly translated or are they modified? How?

initial transcript created from a gene that includes both exons (coding regions) and introns (non-coding regions). It undergoes processing before becoming mature mRNA.

not directly translated; they undergo modifications such as splicing to remove introns, the addition of a 5' cap, and polyadenylation at the 3' end. These modifications are essential to produce mature mRNA, which can be translated into proteins

Define exon and intron and explain RNA processing

the coding sequences in a gene that are retained in the mature mRNA after RNA processing. Exons are expressed and translated into protein.

the non-coding sequences found within a gene that are transcribed into pre-mRNA but are removed during RNA processing. They do not appear in the final mRNA producs

the series of modifications that pre-mRNA undergoes to become mature mRNA. This process includes the addition of a 5' cap, polyadenylation at the 3' end, and splicing to remove introns, allowing the exons to join together.

Explain the importance of alternative splicing

crucial process that allows a single gene to produce multiple protein isoforms by rearranging or including different combinations of exons in the final mRNA transcript. This increases the diversity of proteins that can be expressed from a single gene, enabling a greater range of functional diversity and adaptability in responses to various cellular conditions. Alternative splicing plays a significant role in developmental processes, cellular differentiation, and the regulation of gene expression, contributing to organismal complexity

Describe acetylation of histones

Acetylation of histones involves adding acetyl groups to lysine residues on histone proteins. This neutralizes their positive charge and results in a more relaxed chromatin structure, allowing DNA to be more accessible.

Describe methylation of cytosine and explain the significance

refers to the addition of a methyl group (CH3) to the cytosine base in DNA, typically occurring at cytosines that are followed by guanines (CpG sites). This modification is catalyzed by DNA methyltransferase enzymes.

a crucial role in regulating gene expression by affecting the accessibility of DNA to transcription factors and RNA polymerase. Hypermethylation of gene promoters is often associated with gene silencing, contributing to processes such as genomic imprinting, X-chromosome inactivation, and the development of certain diseases, including cancer. It serves as a key mechanism of epigenetic regulation, influencing cell differentiation and development.

Explain X-inactivation

a process by which one of the two X chromosomes in female mammals is randomly silenced during early embryonic development. This ensures that females, who have two X chromosomes, do not express twice the amount of X-linked genes compared to males, who have only one X chromosome. The inactivated X chromosome condenses into a structure called a Barr body and is largely transcriptionally inactive. X-inactivation occurs early in development and is random, meaning that it can be either

What is meant by epigenetics?

the study of changes in gene expression or cellular phenotype that do not involve alterations to the underlying DNA sequence. These changes can be heritable and are often influenced by environmental factors, lifestyle, and experiences. Key mechanisms of epigenetic regulation include DNA methylation, histone modification, and the action of non-coding RNAs, all of which can significantly impact gene expression and play a role in development, disease, and evolution.

how do DNA methylation patterns compare?

can vary significantly between different cell types, developmental stages, and organisms. Generally, specific genes can exhibit high methylation levels in certain cell types, leading to gene silencing, while those same genes may be unmethylated and actively expressed in others. Additionally, environmental factors, age, and disease states, such as cancer, can alter methylation patterns, influencing gene expression and cellular function.

Explain how regulation of translation can affect gene expression in sea urchin eggs

translation regulation is critical for controlling gene expression during early development. The stored mRNA in the eggs is not immediately translated into proteins; instead, the timing and efficiency of translation can be modified by various factors, including specific RNA-binding proteins and signaling pathways. These regulatory mechanisms ensure that proteins are synthesized at the right time and in the right amounts, allowing for proper embryonic development and cellular differentiation as the fertilized egg begins to divide and form new structures

Define polyubiquitination and explain how it can affect gene expression

process in which multiple ubiquitin molecules are attached to a single target protein, marking it for degradation by the proteasome. This modification signals that the protein is no longer needed or is damaged.

affects gene expression by regulating the abundance and activity of specific proteins involved in transcription, signaling, and other cellular processes. By targeting these proteins for degradation, polyubiquitination can decrease their levels, leading to reduced transcriptional activity of target genes, impacting overall gene expression in the cell.

Explain the role of polyubiquitination in NF kappa B pathway

essential for the activation of IκB kinases (IKKs), which phosphorylate IκB proteins that retain NF kappa B in the cytoplasm. Once IκB is polyubiquitinated, it is targeted for degradation, which allows NF kappa B dimers to translocate to the nucleus and activate the transcription of target genes involved in inflammatory and immune responses

Define cytoplasmic determinant

molecules present within the cytoplasm of a cell that influence the development and differentiation of the cell, often by establishing asymmetries that can lead to cell fate determination during embryonic development.

Define induction

the process by which certain cells or tissues promote the differentiation or developmental changes in neighboring cells or tissues, often involving signaling molecules that influence gene expression and developmental pathways

Explain how vg1 acts as a cytoplasmic determinant

type of cytoplasmic determinant that influences cell fate during embryonic development by establishing positional information and directing the differentiation of neighboring cells. It does this through localized expression and signaling, ultimately affecting gene expression patterns in the cells it influences

Explain what is axis formation

refers to the process during embryonic development where the major body axes of an organism (such as anterior-posterior and dorsal-ventral) are established. This process is crucial for defining the spatial organization of the body plan, influencing the positioning of organs and structures. It involves the coordination of signaling pathways, gene expression, and the actions of cytoplasmic determinants, helping specify cell fates in the developing embryo.

Define homeotic gene

a type of gene that regulates the development of anatomical structures in various organisms, particularly during the embryonic phase. Homeotic genes dictate the identity of body parts and their arrangement along the body axis, ensuring that specific structures develop in the correct locations. Mutations in these genes can result in the transformation of one body part into another, illustrating their crucial role in developmental biology

Explain how bicoid was discovered, how the bicoid mRNA and protein are distributed, and the role of Bicoid

discovered through classical genetic studies and embryological experiments in Drosophila (fruit flies). Researchers identified mutants that displayed anterior-posterior axis defects. These mutations led to the identification of the bicoid gene, which is essential for establishing the head structure in developing embryos.

localized at the anterior end of the Drosophila egg during oogenesis. After fertilization, the mRNA is translated into Bicoid protein, resulting in a gradient of Bicoid protein concentration with higher levels at the anterior pole. This gradient plays a crucial role in determining the anterior-posterior patterning of the embryo.

functions as a transcription factor that activates the expression of target genes involved in anterior development. The gradient of Bicoid protein provides positional information, guiding the formation of the head and other anterior structures during embryonic development.

Explain the role of MyoD in causing the differentiation of myoblasts into muscle fibers

transcription factor that plays a crucial role in the differentiation of myoblasts into muscle fibers. When activated, MyoD binds to specific DNA sequences to initiate the expression of genes involved in muscle-specific functions. This activation leads to changes in the cell's gene expression profile, promoting muscle cell growth, fusion of myoblasts to form multinucleated muscle fibers, and ultimately, the development of mature muscle tissue. MyoD's activity is essential for the myogenic program, ensuring the proper formation of skeletal muscle during development.

Define oncogene and proto-oncogene

A mutated form of a normal gene (proto-oncogene) that has the potential to cause cancer by promoting uncontrolled cell division and growth. Oncogenes arise from mutations that lead to an overexpression or hyperactivity of the proteins they encode

A normal gene that plays a role in cell growth and division. Proto-oncogenes can become oncogenes when mutated or expressed at high levels, leading to the potential development of cancer.

Explain how protein overexpression or absence of a protein can lead to cancer

can lead to continuous and unregulated cell division, promoting cancerous changes. Conversely, the absence of tumor suppressor proteins can remove the checks on cell division, allowing for unchecked growth and contributing to the development of cancer.

Define polyp

a benign growth that occurs on mucosal surfaces, often found in organs such as the colon. Polyps can vary in size and shape and may be pedunculated (with a stalk) or sessile (flat). While many polyps are harmless, some may develop into cancer over time, making regular monitoring important.

Explain why colon cancer is slow growing and how to catch colon cancer early

typically slow growing due to the gradual accumulation of genetic mutations over time, often starting from benign polyps that may take years to develop into malignant tumors. This indolent progression allows for cellular changes and adaptations that may not immediately result in aggressive cancerous behavior.

Define ras and explain how mutation of ras contributes to cancer

a family of related proteins that act as molecular switches in various signaling pathways, primarily involved in the control of cell growth, differentiation, and survival.

Mutations in the ras gene can lead to the production of a continuously active Ras protein that promotes uncontrolled cell division and growth. These mutations often result in the inability of the protein to hydrolyze GTP, keeping Ras in an active state and signaling the cell to proliferate without the usual regulatory checks, contributing to cancer development.

Explain the function of P53 and explain how defective or missing p53 can contribute to cancer

a crucial tumor suppressor protein that plays a key role in regulating the cell cycle, maintaining genomic stability, and initiating DNA repair processes. It can trigger apoptosis (programmed cell death) in cells with irreparable damage, effectively acting as a guardian of the genome.

is defective or absent, cells lose their ability to regulate the cell cycle and undergo apoptosis effectively. This loss leads to the accumulation of genetic mutations, unchecked cell division, and ultimately contributes to the development and progression of cancer.

Genetic mutations contribution towards cancer

can lead to alterations in the DNA sequence that may disrupt normal cell function, promote uncontrolled cell growth, and impair the mechanisms that regulate the cell cycle. These mutations can be inherited or acquired through environmental factors, leading to oncogene activation, tumor suppressor gene inactivation, and failure of DNA repair processes, all of which are pivotal in the initiation and progression of cancer.

Exposure to DNA damaging agents contribution towards cancer

can lead to genetic mutations that disrupt normal cellular functions. These mutations may result in the activation of oncogenes or inactivation of tumor suppressor genes, increasing the risk of uncontrolled cell growth and division. Additionally, DNA damage can impair the DNA repair mechanisms, allowing further mutations to accumulate, which can ultimately contribute to the development and progression of cancer.

viruses contribution towards cancer

can contribute to cancer development through various mechanisms, such as integrating their genetic material into the host genome, which can disrupt normal cellular functions and lead to uncontrolled cell growth. Certain oncogenic viruses, like human papillomavirus (HPV), Epstein-Barr virus (EBV), and hepatitis B virus (HBV), produce proteins that interfere with tumor suppressor mechanisms and promote cell proliferation. Additionally, chronic viral infections can cause inflammation and immune system evasion, further increasing the risk of cancer development.

How can Translocation or transposition cause a proto-oncogene to become an oncogene

can lead to the conversion of a proto-oncogene into an oncogene by relocating the proto-oncogene to a different chromosomal location where it is placed under the control of a highly active promoter. This can result in increased expression of the proto-oncogene or create a fusion gene that encodes a hybrid protein with enhanced activity, consequently promoting uncontrolled cell growth and division.

How Gene amplification cause a proto-oncogene to become an oncogene

can cause a proto-oncogene to become an oncogene by increasing the number of copies of that proto-oncogene within the genome. This results in overexpression of the gene product, typically a protein that promotes cell growth and division, leading to uncontrolled cell proliferation and the potential development of cancer.

How Point mutation in a control element cause a proto-oncogene to become an oncogene

can cause a proto-oncogene to become an oncogene by altering the regulatory sequences that control its expression. This alteration can result in increased expression of the proto-oncogene or change its responsiveness to regulatory signals, leading to the overproduction of its protein product. Such overexpression can drive uncontrolled cell division and contribute to tumor development.

How Point mutation within a gene cause a proto-oncogene to become an oncogene

can transform a proto-oncogene into an oncogene by directly altering the coding sequence, which may lead to a gain of function. This results in the production of a protein that is constitutively active or overactive, driving uncontrolled cell growth and division, ultimately contributing to cancer development.

How can Increased level or activity of proteins that stimulate cell division contribute to cancer

can lead to uncontrolled cell proliferation, disrupting normal regulatory mechanisms. This overactivity can result in excessive and unregulated growth, significantly increasing the risk of tumor development and cancer progression.

How can Losing the function of tumor suppressor genes that repair DNA or function as checkpoints contribute to cancer

can lead to cancer by removing critical controls on cell division and maintaining genomic integrity. When these genes are dysfunctional, cells may accumulate mutations and genetic instability without the necessary halting mechanisms, allowing for uncontrolled cell proliferation. This unchecked growth can ultimately culminate in the development of cancer.

How can Failure of the immune system contribute to cancer

can contribute to cancer by diminishing the body's ability to recognize and eliminate cancerous cells. When the immune response is weak or impaired, it allows tumor cells to evade detection and proliferation, leading to increased tumor growth and the potential development of cancer.

Describe deacetylation of histones

- Deacetylation is the removal of acetyl groups from the histones, which restores the positive charge on lysines. This leads to a tighter chromatin structure, making the DNA less accessible.

How do acetyl groups affect DNA accessibility for transcription?

The presence of acetyl groups on histones allows the DNA to loosen up, which is crucial for transcription to occur. When the DNA is tight and compact, like the way you might feel when stress piles up, it's hard for the necessary proteins to access the information they need to function.