Regulation of Gene Expression and Operon Model

Regulation of Gene Expression

• Differential gene expression results in different cell types, each carrying out specific functions.
• Each gene requires specific transcription factors, leading to varied expression across different cells.

Bacterial Response to Environmental Change

• Bacteria regulate transcription in response to environmental changes.
• Natural selection favors bacteria that only express genes encoding products needed by the cell.
• Cells can regulate enzyme production through feedback inhibition or gene regulation.
• Feedback inhibition involves the end product of a metabolic pathway inhibiting enzyme activity to halt further production.
• Cells adjust enzyme production by regulating the expression of genes encoding these enzymes.
• Control of enzyme production occurs at the level of transcription.

Operon Model

• The operon model is a basic mechanism for regulating groups of genes.
• Functionally related genes are coordinately controlled by an "on-off switch".
• The operator, a DNA segment, acts as the switch, located within the promoter or between the promoter and enzyme-coding genes.
• An operon includes the operator, promoter, and genes they control.
• The operon can be switched off by a repressor protein.
• The repressor prevents gene transcription by binding to the operator, blocking RNA polymerase.
• A regulatory gene, separate from the operon, produces the repressor.
• Repressors exist in active or inactive forms, depending on molecule presence.
• A corepressor is a molecule that helps a repressor protein switch an operon off.
• E. coli synthesizes tryptophan if it is deficient.

trp Operon

• The trp operon is on by default, allowing tryptophan synthesis genes to be transcribed.
• Tryptophan binds to the trp repressor protein when present, turning the operon off.
• The repressor is active only with its corepressor, tryptophan.
• High tryptophan levels turn off (repress) the trp operon.

Repressible and Inducible Operons

• Repressible operons are usually on; repressor binding shuts off transcription (trp operon).
• Inducible operons are usually off; an inducer molecule inactivates the repressor and turns on transcription.

lac Operon

• The lac operon is an inducible operon containing genes coding for lactose hydrolysis and metabolism enzymes.
• The transcription unit is controlled by one main operator and promoter.
• A regulatory gene, lacl, outside the operon, encodes a repressor protein that can switch off the operon.
• The lac repressor is active by itself, switching the lac operon off.
• An inducer molecule inactivates the repressor to turn the lac operon on.
• Allolactose, a lactose isomer, is the inducer in the lac operon.
• Allolactose binds the repressor protein, changing its shape, preventing binding to the operator sequence.
• Some function in catabolic pathways where synthesis gets induced by a chemical signal
• Repressible enzymes typically have catabolic pathways and their synthesis is repressed by high levels of end product
• Regulation of the operons involves negative control of genes, and they get shut down by the active repressor

Positive Gene Regulation

• Some operons undergo positive control via a stimulatory protein, such as cyclic AMP receptor protein (CRP), an activator of transcription.
• When glucose (E. coli's preferred food) is scarce, CRP gets by binding with cyclic AMP (cAMP).
• Activated CRP attaches to the lac operon promoter, enhancing RNA polymerase affinity and transcription.
• CRP detaches when glucose levels rise, with transcription returning to a low level.
• CRP regulates other operons that encode enzymes in catabolic pathways.
• Catalyzing compounds like lactose enables cells deprived of glucose to survive.
• Cell compounds determine which genes are switched on

Eukaryotic Gene Expression

• Eukaryotic gene expression is regulated at many stages
• All organisms regulate gene expression
• Genes go on and off from internal and external stimuli
• In multicellular organisms, regulation of gene expression is essential

Differential Gene Expression

• Virtually organisms contain cells with the same genome
• Cell differences results from differential gene expression
• Abnormalities in gene expression can lead to diseases including cancer
• Gene expression is regulated by transcription

Chromatin Structure

• The structural organization of chromatin affect gene expression
• Genes in heterochromatin are not usually expressed
• Gene transcription in euchromatin is impacted by the location of nucleosomes, where the DNA attaches to the scaffolding of the chromosome of the protein
• influenced from alterations in the histone proteins of the nucleosome
• Changes are catalyzed by enzymes

Histone Modifications and DNA Methylation

• Acetyl groups attach to an amino acid in a histone tail in histone acetylation
• Chromatin structure can open up, leading to the beginning of transcription
• Methyl groups can be added to condense and reduce transcription

DNA methylation

• DNA methylation has methyl groups added to certain DNA basses and causes reduced transcription
• It can cause long-term inactivation of the genes during cell differentiation
• Genomic imprinting causes the methylation to regulates expression of either of the parents

Epigenetic inheritance

• Inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence
• Can explain why one twin has a disease and another doesn't

Regulation of Transcription Initiation

• Chromatin-modifying enzymes affects if the region in the DNA is more or less likely to bind the machinery

Eukaryotic Genes and Expression

• These genes are have many control segments of noncoding DNA that act as binding sites
• Control segments and all transcription factors are important to regulation in different cell types

Gene Transcription

• RNA polymerase II needs assistance from all transcription factors to start transcription
• TATA box needs to bind to transcription factor Transcription factors depend on certain elements at certain times or factors
• RNA polymerase needs to assemble in order to move through the DNA strand
• Genes can be transcribed from different locations

Specific Transcription

• Proximal control elements need are near the promoter
• Distal control elements have groups of proteins called enhancers
• Enhancers have one and only one gene
• Activators bond to the DNA strand

Mediators

• Protein bending is required to bound activators
• Mediators interacts with transcription factors at the promoter
• This helps assemble the complex

Repressors

• Can stop expression by several ways
• Some repressors bonds to the activator block
• Some may affect transcription by changing chromatin structure'

Combinatorial Control

• Only the proteins present can activate transcription
• Only a small number of control elements are needed

Coordinately Controlled Genes

• They are not organized in operons
• These genes are spread across different chromosomes to have the same control elements
• Activator proteins recognize the control and start expressing the genes

Post-Transcriptional Regulation

• Transcription alone does not constitute gene expression
• Happens in after transcription
• Helps make it so a cell can actively change gene expression

RNA Processing

• Alternative RNA splicing causes primary transcripts to produce multiple different molecules
• Eukaryotic genome expands because of Alternative RNA splicing
• Less genes exists in humans because of it
• Proteins code with alternative splicing at 90 percent

Initiation of Translation and mRNA Degradation

• Regulatory proteins stop certain proteins produced by the mRNA
• All of the mRNA translation is controlled at the same time
• Eggs get fertilization by activation simultaenously

mRNA Half Life

• Molecules are important
• mRNA has a longer half-life in Eukaryotic's
• The regions at in the RNA's has influence on it's lifespan

Protein Processing and Degradation

• Polypeptides have to undergo processing, and modifications
• Cells have to mark the proteins so it can be degraded
• Proteins get degraded

Noncoding RNAs Control Gene Expression

• Gene code consists of small fractions of DNA for proteins
• These genes that did not encode a protein were "junk DNA"
• Studies have shown genomic evidence towards this
• ncRA's roles in biology are being uncovered
• This has changed biologists mindset

MicroRNAs

• MicroRNA's can bind to mRNA sequences
• They cause degradation, or block it from translation
• Expression of human genes estimate that there is half that genes controlled through microRNA

Interfering RNA

• They are similar to microRNA's
• Genes getting genes getting blocked are called RNA interference
• This is used in the laboratory so that the genes functions can be understood
• Used by bacteria for RNA, they have the defense system against viruses called the CRISPR-Cas9

Chromatin Remodeling

• They use ncRNA's
• Structure and transcription are impacted
• SiRNA can reform heterochromatin
• Many don't have siRNA, so the mechanism is mostly unknown

Long noncoding RNAs

• They stretch from 200 to hundreds of nucleotides
• One is responsible for X chromosome inactivation
• Transcription affects how genes get exposed
• Scaffolding can bring DNA, proetines, and RNAs altogether
• Development of embryo's are the peak of gene expression

Embryonic Gene Expression Program

• Embryonic development has differentiated genes
• Organize into tissues, to whole organisms
• Gene expression does the developmental programs

Genetic Program for Development

• Stem from cell division, cell differentiation, and morphogenesis
• Cells have the to specialize into structure and function because of cell differentiation
• Physical things have to be in place to result in morphogenesis.

Cytoplasmic Determination

• Cytoplasms have RNA, proteins, and other substances that's uneven
• Embryo has cells different due to cytoplasmic determination
• Signal molecules can cause nearby targets to change
• Interacting cells lead to differentiation

Gene Expression Regulation

• Determination has cells with different characteristics
• Cells are embryonic and differentiate on their normal route
• How to activate cell growth

Model

• Changes to molecular cause tissue exposure
• MRNA changes
• Multiple steps causes regulation

Myoblasts

• Muscle cells are the outcome with the cells being determined
• One gene has a code for it and transcription that makes it muscle
• Additional target cells do have transcription

Body Plan Setting

• How tissues and organs structure
• This is built by the major axes
• Positioned information is dependent of the locations of the cells

Pattern Formation

• Studies done from fruit flys
• People discovered principles that are very common within species
• Flys are constructed with modular constructs
• Early development done from mother bicoid gene
• This is essential to setting up setting up setting up the embryo
• This hypothesis is to do with the gradients and its morphogens

Bicoid mRNA

• The morphogen determined by the the head structures

Three Reasons for Bicoid

• The specific protein was required for early patters
• Increased understanding of mothers role
• Determine gradient form from anterior to posterior

Cancer

• Gene regulations do go wrong, but are also the same systems involved in development

Type of Gene

Mutations:

• Proto-oncogenes become oncogenes Tumor-suppressor Inherit: Epigenetic Translocation
• amplifications Point

Cell-Signaling Pathways

• Ras can lead to increase of more cell and cause division
• Growth factors lead to cell division
• P53 gene doesn't get compressed with mutations
• Cancer rare with Elephants at 3%-10%
• Elephant sequencing with 20-40%

Multistep Development Model

• Incidences from the age
• A cell has an active proto agent that helps with several suppression

Colon

• Routine screenings
• Polypeptides needed after progresses
• Genes help detect and attack tumors

Explore differential gene expression leading to diverse cell types and functions. Understand how bacteria regulate transcription in response to environmental changes, using mechanisms like feedback inhibition and gene regulation to control enzyme production and expression.