BIOL. 1406 Chapter 18 Regulation of Gene Expression Flashcards
How can two cells with the same set of genes function differently?
To be expressed, each gene requires a particular set of transcription factors.
Differential Gene Expression
The expression of different genes, allowing cells to carry their specific function.
Regulation of enzyme production by a cell
feedback inhibition and gene regulation
Feedback Inhibition
The end product of metabolic pathway shuts down further synthesis of the product by inhibiting enzyme activity.
Regulating Gene Expression
Adjusting production level of certain enzymes by a cell;
the control of enzyme production is thus at the level of transcription
Operon
the entire stretch of DNA that includes the operator, the promoter, and the genes that they control
Operator
A segment of DNA that acts as an on-off switch that can coordinate a cluster of functionally related genes
Repressor
A protein that switches off the operon;
it prevents gene transcription by binding to the operator and blocking RNA polymerase;
can be in an active or inactive form, depending on the presence of other molecules.
Regulatory Gene
A gene that is located some distance from the operon itself and produces the repressor protein
Corepressor
A molecule that cooperates with a repressor protein to switch an operon off.
Activator
A stimulatory protein that are used in positive control
Eukaryotic Gene Expression Is Regulated At Many Stages
all organisms must regulate which genes are expressed at any given time;
genes are turned off and on in response to the internal and external environments;
in multicellular organisms, regulation of gene expression is essential for cell specialization
Differential Gene Expression
Expression of different genes by cells with the same genome;
most of the time is equated with gene transcription
Chromatin
makeup of chromosomes in organisms other than bacteria; it includes DNA, RNA, and protein.
Expression Regulation by Chromatin Structure
The structural organization of chromatin helps regulate gene expression in several ways;
genes within highly packed heterochromatin are usually not expressed;
in euchromatin, gene transcription is affected by the location of nucleosomes;
chromatin structure and gene expression can be influenced by chemical modifications of the histone proteins on the nucleosome
Euchromatin
A lightly packed form of chromatin that is enriched in genes, and is often under active transcription
Nucleosome
a structural unit of a eukaryotic chromosome, consisting of a length of DNA coiled around a core of histones
Histone Acetylation
Acetyl groups are attached to an amino acid in a histone tail.
This appears to open up chromatin structure, thus promoting the initiation of transcription.
DNA Methylation
Addition of methyl groups to certain DNA bases;
associated with reduced transcription;
can cause long-term inactivation of genes in cellular differentiation;
Can change the activity of a DNA segment without changing the sequence
Epigenetic Inheritance
inheritance of traits transmitted by mechanisms not directly involving the nucleoside sequence
Control Elements
Segments of noncoding DNA that serve as binding sites for transcription factors that help regulate transcription
Specific Transcription Factors
A different set of factors that high levels of transcription depend on for genes that are not expressed all the time
Proximal Control Elements
Control elements that are located close to the promoter
Enhancers
distal control elements, groupings that may be far away from the gene or even located in an intron;
each enhancer is associated with only one gene and no other
Activator
a protein that binds to an enhancer and stimulates the transcription of a gene;
has two domains: one binds to DNA and the other one that activates the transcription;
bound activators facilitate a sequence of protein-protein interactions that result in enhanced transcription of a given gene
Mediator proteins
A group of proteins that that interact with general transcription factors at the promoter;
they come into contact with bound activators;
this helps assembly and position the preinitiation complex.
Transcription Factors in Gene Expression
Some act as repressors, inhibiting expression of a particular gene in several ways;
some repressors bind directly to control elements and block activator binding;
others interfere with activators, so they cannot bind the DNA;
some activators and repressors may indirectly affect transcription by altering chromatin structure.
Combinatorial Control of Gene Activation
A particular combination of control elements can activate transcription only when the appropriate activator proteins are present;
with only a dozen or so control elements, a large number of potential combinations is possible
Coordinately Controlled Genes in Eukaryotes
Co-expressed eukaryotic genes are not organized in operons (with a few exceptions);
these genes can be scattered over different chromosomes, but each has the same combination of control elements;
activator proteins in the nucleus recognize specific control elements and promote simultaneous transcription of genes
Mechanisms of Post-Transcriptional Regulation
Transcription alone does not constitute gene expression;
regulatory mechanisms can operate at various stages after transcription;
such mechanisms allow a cell to rapidly fine-tune gene expression in response to environmental changes
Alternative Splicing
different RNA molecules are produced from the same primary transcript, depending on which RNA segments are treated as exons and which introns;
it significantly expands the repertoire of a eukaryotic genome;
proposed explanation for the surprisingly low number of genes in the human genome;
more than 90% of the human protein-coding genes undergo alternative splicing
Initiation of translation
can be blocked by regulatory proteins that bind to sequences or structures of the mRNA;
may be regulated simultaneously
Protein Processing and Degradation
after translation, polypeptides undergo processing and chemical modifications;
the length time each protein functions is regulated by selective degradation;
cells mark proteins for degradation by attaching ubiquitin to them;
the mark is recognized by proteasomes, which recognize and degrade proteins
MicroRNAs (miRNAs)
small, single-stranded RNA molecules that can bind complementary sequences in mRNA;
these molecules along with associated proteins cause degradation of the target mRNA or sometimes block its translation;
at least one half of genes may be regulated by miRNAs
Small Interfering RNAs (siRNAs)
similar to miRNAs in size and function;
used in laboratory as means of disabling genes to investigate their function;
used by bacteria as a defensive system, called CRISPR-Cas9 system, against viruses that infect them
RNA Interference
blocking of gene expression by siRNAs
Chromatin Remodeling and Effects on Transcription by ncRNAs
some ncRNA can cause remodeling of chromatin structure;
in some yeasts, siRNAs reform heterochromatin at centromeres after chromosome replication;
in most mammalian cells, siRNAs have not been found
piwi-interacting RNAs (pRNAs)
small ncRNAs induce formation of heterochromatin, blocking the expression of parasitic DNA elements in the genome known as transposons;
help reestablish appropriate methylation patterns during gamete formation in many animal species
Long noncoding RNAs (lncRNAs)
range from 200 to hundreds of thousands nucleotides in length;
one type is responsible for inactivation of the X chromosome;
can act as a scaffold, bringing DNA, proteins, and other RNAs together into complexes, promoting gene expression
A program of differential gene expression
orchestrates the developmental programs of animals;
during embryonic development, a fertilized egg gives rise to many different types of cell;
cells are organized successfully into tissues, organs, organ systems, and organisms
Genetic Program for Embryonic Development
transformation from zygote to an adult results from cell division, cell differentiation, and morphogenesis
Cell differentiation
the process by which cells become specialized in structure and function;
a cell attains its determined fate
Morphogenesis
the physical processes that give an organism its shape
Cytoplasmic Determinants
maternal substances in the egg that influence early development;
as cells divides by mitosis, cells contain different cytoplasmic determinants, which lead to different gene expression
Induction
a process, in which signal molecules from embryonic cells cause changes in the nearby target cells
Determination
irreversibly commits a cells to become of particular type
MyoD
a master regulatory gene that encodes a transcription factor that commits the cell to becoming skeletal muscle;
some encode information for production of additional muscle-specific transcription factors
Pattern Formation
development of spatial organization of tissues and organs;
begins with the establishment of major axes
Positional Information
molecular cues that control pattern formation, tells a cell its location relative to the body axes and neighboring cells
Homeotic genes
genes that control pattern formation in the late embryo, larva, and adult stages in drosophila melanogaster
Embryonic Lethals
mutations that cause death during embryogenesis
Maternal Effect Genes
encode cytoplasmic determinants that initially establish the axes of the body of the drosophila
Bicoid
one maternal effect gene that affects the front half of the body
Morphogens
gradients of substances that establish an embryo’s axes and other features of its form
Oncogenes
Genes, resulted from mutations in proto-oncogenes;
(proto-oncogenes code for proteins in regular cell growth and division);
arises from a change that leads to an increase either in the amount of protein product or in the activity of protein molecule
genetic changes that convert proto-oncogenes into oncogenes
1) epigenetic changes 2) translocation 3) gene amplification 4) point mutations
Tumor-suppressor genes
normally inhibit cell division;
mutations to these genes decrease protein products and contribute to cancer onset;
normally repair damaged DNA, control cell adhesion, and act in cell-signaling pathways that inhibit the cell cycle
Interference with Normal Cell-Signaling Pathways
Mutations in the ras proto-oncogene and p53 tumor-suppressor gene are common in human cancers
Ras gene
mutations in it can produce hyperactive ras protein and increased cell division
Ras protein
a G protein that relays a signal from a growth factor receptor on the cell surface
p53 gene
mutations in it prevent suppression of the cell cycle;
suppression of the cell cycle can be important in the case of damage to a cell’s DNA;
its normal version prevents a cell from passing on mutations;
it activates expression of miRNAs that inhibit the cell cycle, and can turn on genes directly involved in DNA repair;
it activates cell “suicide” genes;
elephants have 20 copies of p53 gene compared to just 1 copy in humans and other mammals (elephants have very low cancer rates 3%)
The Multi-Step of Cancer Development
multiple mutation are generally needed for full-fledge cancer; incidents increase with age;
a DNA level, a cancerous cell is usually characterized by at least one oncogene and the mutation of several tumor-suppressor genes
Inherited Predisposition and Environmental Factors Contributing to Cancer
Individuals can inherit oncogenes or mutant alleles of tumor-suppressor genes
Adenomatous Polyposis Coli
tumor suppressor gene;
inherited mutations of it are common in individuals with colorectal cancer
Mutations in the BRCA1 and BRCA2 genes
mutations found in at least half of inherited breast cancers, and tests using DNA sequencing can detect these mutations
The role of viruses in cancer
a number of tumor viruses can also cause cancer in humans and animals;
viruses can interfere with normal gene regulation in several ways if they integrate into the DNA of a cell;
viruses are powerful biological agents
General Transcription Factors
Factors that are essential for transcription of all protein-coding genes;
Their assistance is required by RNA Polymerase II to initiate transcription
