Chapter 18- Lecture Outline Flashcards
Prokaryotes and eukaryotes precisely regulate gene expression in response to environmental conditions
In multicellular eukaryotes, gene expression regulates development and is responsible for differences in cell types
RNA molecules play many roles in regulating gene expression in eukaryotes
Natural selection has favored bacteria that produce only the products needed by that cell
A cell can regulate the production of enzymes by feedback inhibition or by gene regulation
One mechanism for control of gene expression in bacteria is the operon model
A cluster of functionally related genes can be coordinately controlled by a single “on-off switch”
The “switch” is a segment of DNA called an operator usually positioned within the promoter
______________ is the entire stretch of DNA that includes the operator, the promoter, and the genes that they control
operon
The operon can be switched off by a protein repressor
The repressor 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 corepressor is a molecule that cooperates with a repressor protein to switch an operon off
For example, E. coli can synthesize the amino acid tryptophan when it has insufficient tryptophan
By default the trp operon is on and the genes for tryptophan synthesis are transcribed
When tryptophan is present, it binds to the trp repressor protein, which turns the operon off
The repressor is active only in the presence of its corepressor tryptophan; thus the trp operon is turned off (repressed) if tryptophan levels are high
A repressible operon is one that is usually on; binding of a repressor to the operator shuts off transcription
The trp operon is a repressible operon
An inducible operon is one that is usually off;a molecule called an inducer inactivates the repressor and turns on transcription
The lac operon is an inducible operon and contains genes that code for enzymes used in the hydrolysis and metabolism of lactose
By itself, the lac repressor is active and switches the lac operon off
A molecule called an inducer inactivates the repressor to turn the lac operon on
Inducible enzymes usually function in catabolic pathways; their synthesis is induced by achemical signal
Repressible enzymes usually function in anabolic pathways; their synthesis is repressed by high levels of the end product
Regulation of the trp and lac operons involves negative control of genes because operons are switched off by the active form of the repressor
Some operons are also subject to positive control through a stimulatory protein, such as catabolite activator protein (CAP), an activator of transcription
When glucose (a preferred food source of E. coli) is scarce, CAP is activated by binding with cyclic AMP (cAMP) Activated CAP attaches to the promoter of the lac operon and increases the affinity of RNA polymerase, thus accelerating transcription
When glucose levels increase, CAP detaches from the lac operon, and transcription returns to a normal rate
CAP helps regulate other operons that encode enzymes used in catabolic pathways
All organisms must regulate which genes are expressed at any given time
In multicellular organisms regulation of gene expression is essential for cell specialization
Almost all the cells in an organism are genetically identical
Differences between cell types result from differential gene expression, the expression of different genes by cells with the same genome
Abnormalities in gene expression can lead to diseases including cancer
Gene expression is regulated at many stages
The structural organization of chromatin helps regulate gene expression in several ways
Genes within highly packed heterochromatin are usually not expressed
Chemical modifications to histones and DNA of chromatin influence both chromatin structure and gene expression
In histone acetylation, acetyl groups are attached to positively charged lysines in histone tails
This 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, 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
Although the chromatin modifications just discussed do not alter DNA sequence, theymay be passed to future generations of cells
The inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence is called epigenetic inheritance
Chromatin-modifying enzymes provide initial control of gene expression by making a region of DNA either
more or less able to bind the transcription machinery
Associated with most eukaryotic genes are multiple control elements, segments of noncoding DNA that serve as binding sites for transcription factors that help regulate transcription
Control elements and the transcription factors they bind are critical to the precise regulation of gene expression in different cell types
To initiate transcription, eukaryotic RNA polymerase requires the assistance of transcription factors
General transcription factors are essential for the transcription of all protein-coding genes
In eukaryotes, high levels of transcription of particular genes depend on control elements interacting with specific transcription factors
Proximal control elements are located close tothe promoter
Distal control elements, groupings of which are called enhancers, may be far away from a geneor even located in an intron
An activator is a protein that binds to an enhancer and stimulates transcription of a gene
Activators have two domains, one that binds DNA and a second that activates transcription
Bound activators facilitate a sequence of protein-protein interactions that result in transcription of a given gene
Some transcription factors function as repressors, inhibiting expression of a particular gene by a variety of methods
Some activators and repressors act indirectly by influencing chromatin structure to promote or silence transcription
A particular combination of control elements
can activate transcription only when the appropriate activator proteins are present
Co-expressed eukaryotic genes are not organized in operons (with a few minor exceptions)
These genes can be scattered over different chromosomes, but each has the same combination of control elements
Copies of the activators recognize specific control elements and promote simultaneous transcription of the genes
Loops of chromatin extend from individual chromosome territories into specific sites in the nucleus
Loops from different chromosomes may congregate at particular sites, some of which are rich in transcription factors and RNA polymerases
These may be areas specialized for a common function
Transcription alone does not account for gene expression
Regulatory mechanisms can operate at various stages after transcription
Such mechanisms allow a cell to fine-tune gene expression rapidly in response to environmental changes
In alternative RNA splicing, different mRNA molecules are produced from the same primary transcript,
depending on which RNA segments are treated as exons and which as introns
The initiation of translation of selected mRNAs can be blocked by regulatory proteins that bind to sequences or structures of the mRNA
Alternatively, translation of all mRNAs in a cell may be regulated simultaneously
For example, translation initiation factors are simultaneously activated in an egg following fertilization
The life span of mRNA molecules in the cytoplasm is a key to determining protein synthesis
Eukaryotic mRNA is more long lived than prokaryotic mRNA
Nucleotide sequences that influence the lifespan of mRNA in eukaryotes reside in the untranslated region (UTR) at the 3′ end of the molecule
After translation, various types of protein processing, including cleavage and the additionof chemical groups, are subject to control
The length of time each protein function is regulated by selective degradation
Cells mark proteins for degradation by attaching ubiquitin to them
This mark is recognized by proteasomes, which recognize and degrade the proteins
Only a small fraction of DNA codes for proteins, and a very small fraction of the non-protein-coding DNA consists of genes for RNA such as rRNAand tRNA
A significant amount of the genome may be transcribed into noncoding RNAs (ncRNAs)
Noncoding RNAs regulate gene expression attwo points: mRNA translation and chromatin configuration
MicroRNAs (miRNAs) are small single-stranded RNA molecules that can bind to mRNA
These can degrade mRNA or block its translation
It is estimated that expression of at least half of all human genes may be regulated by miRNAs
Small interfering RNAs (siRNAs) are similar to miRNAs in size and function
The blocking of gene expression by siRNAs is called RNA interference (RNAi)
RNAi is used in the laboratory as a means of disabling genes to investigate their function
Some ncRNAs act to bring about remodeling of chromatin structure
In some yeasts siRNAs re-form heterochromatin at centromeres after chromosome replication
Small ncRNAs called piwi-associated RNAs (piRNAs) induce heterochromatin, blocking the expression of parasitic DNA elements in
the genome, known as transposons
RNA-based regulation of chromatin structure is likely to play an important role in gene regulation
Small ncRNAs can regulate gene expressionat multiple steps
An increase in the number of miRNAs in a species may have allowed morphological complexity to increase over evolutionary time
siRNAs may have evolved first, followed by miRNAs and later piRNAs
During embryonic development, a fertilized egg gives rise to many different cell types
Cell types are organized successively into tissues, organs, organ systems, and the whole organism
Gene expression orchestrates the developmental programs of animals
The transformation from zygote to adult results from cell division,
cell differentiation, and morphogenesis
Cell differentiation is the process by which cells become specialized in structure and function
The physical processes that give an organism its shape constitute morphogenesis
Differential gene expression results from genes being regulated differently in each cell type
Materials in the egg set up gene regulation that is carried out as cells divide
An egg’s cytoplasm contains RNA, proteins, and other substances that are distributed unevenly in the unfertilized egg
Cytoplasmic determinants are maternal substances in the egg that influence early development
As the zygote divides by mitosis, cells contain different cytoplasmic determinants, which lead to different gene expression
The other important source of developmental information is the environment around the cell, especially signals from nearby embryonic cells
In the process called induction, signal molecules from embryonic cells cause transcriptional changes in nearby target cells
Thus, interactions between cells induce differentiation of specialized cell typesThus, interactions between cells induce differentiation of specialized cell types
Determination irreversibly commits a cell to its final fate
Determination precedes differentiation
Cell differentiation is marked by the production of tissue-specific proteins
Myoblasts are cells determined to produce muscle cells and begin producing muscle-specific proteins
MyoD is a “master regulatory gene” encodes a transcription factor that commits the cell to becoming skeletal muscle
The MyoD protein can turn some kinds of differentiated cells—fat cells and liver cells—into muscle cells
Pattern formation is the development of a spatial organization of tissues and organs
In animals, pattern formation begins with the establishment of the major axes
Positional information, the molecular cues that control pattern formation, tells a cell its location relative to the body axes and to neighboring cells
Pattern formation has been extensively studied in the fruit fly Drosophila melanogaster
Combining anatomical, genetic, and biochemical approaches, researchers have discovered developmental principles common to many other species, including humans
In Drosophila, cytoplasmic determinants in the unfertilized egg determine the axes before fertilization
After fertilization, the embryo develops into a segmented larva with three larval stages
Edward B. Lewis, Christiane Nüsslein-Volhard, and Eric Wieschaus won a Nobel Prize in 1995 for decoding pattern formation in Drosophila
Lewis discovered the homeotic genes, which control pattern formation in late embryo, larva, and adult stages
Nüsslein-Volhard and Wieschaus studied segment formation
They created mutants, conducted breeding experiments, and looked for corresponding genes
Many of the identified mutations were embryonic lethals, causing death during embryogenesis
They found 120 genes essential for normal segmentation
Maternal effect genes encode cytoplasmic determinants that initially establish the axes
of the body of Drosophila
These maternal effect genes are also called egg-polarity genes because they control orientation of the egg and consequently the fly
One maternal effect gene, the bicoid gene, affects the front half of the body
An embryo whose mother has no functional bicoid gene lacks the front half of its body and has duplicate posterior structures at both ends
This phenotype suggests that the product of the mother’s bicoid gene is essential for setting up the anterior end of the embryo
This hypothesis is an example of the morphogen gradient hypothesis, in which gradients of substances called morphogens establish an embryo’s axes and other features of its form
Experiments showed that bicoid protein is distributed in an anterior to posterior gradient in the early embryo
The bicoid research was ground breaking for three reasons
It identified a specific protein required for some early steps in pattern formation
It increased understanding of the mother’s role in embryo development
It demonstrated a key developmental concept that a gradient of molecules can determine polarity and position in the embryo
