Chapter 18 - Regulation of Gene Expression

Question 1

How do bacteria respond to environmental changes?

Answer 1

By regulating transcription; 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

Question 2

What is an operator?

Answer 2

A cluster of functionally related genes can be controlled by a single “on-off switch”; the “switch” is a segment of DNA called an operator, usually positioned within the promoter

The operator controls the access of RNA polymerase to the genes

Question 3

What is an operon?

Answer 3

Altogether, the operator (on off switch), the promoter (the places where RNA polymerase binds), and the genes they control, constitute an operon

• 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

Question 4

What is the repressor?

Answer 4

The operon can be switched off by a protein that is called the trp repressor; the repressor prevents gene transcription by binding to the operator and blocking RNA polymerase

A repressor protein is specific for the operator of a particular operon

The repressor can be in an active or inactive form, depending on the presence of other molecules;

The repressor is active only in the presence of its corepressor tryptophan; thus the trp operon is turned off if tryptophan levels are high

Question 5

What is the regulatory gene?

Answer 5

The trp repressor is the protein product of a regulatory gene called trpR, which is located some distance from the trp operon and has its own promoter; regulatory genes are expressed continuously, although at a low rate

Question 6

What is a corepressor?

Answer 6

A small molecule that cooperates with a repressor protein to switch an operon off

i.e. E. coli can synthesize the amino acid tryptophan when it has insufficient tryptophan

Question 7

What is a repressible operon?

Answer 7

One that is usually on but can be inhibited when the binding of a repressor to the operator shuts off transcription

The trp operon is a repressible operon

Question 8

What is an inducible operon?

Answer 8

Usually off but can be stimulated when a molecule called an inducer inactivates the repressor and turns on transcription

The lac operon in an inducible operon and contains genes that code for enzymes used in the hydrolysis and metabolism of lactose

Question 9

What is an inducer?

Answer 9

A specific small molecule that inactivates the repressor (to turn the lac operon on)

Question 10

What are inducible enzymes?

Answer 10

Inducible enzymes usually function in catabolic pathways; their synthesis is induced by a chemical signal

Question 11

What are repressible enzymes?

Answer 11

Repressible enzymes function in anabolic pathways; their synthesis is repressed by high levels of the end product

Question 12

What is an activator?

Answer 12

A protein that binds to DNA and stimulates transcription of a gene

Some operons are subject to positive control through a stimulatory protein, such as catabolite activator protein (CAP); when glucose (preferred food source of E. coli) is scarce, CAP is activated by binding with cyclic AMP (cAMP); activated CAP attached to the promotor of the lac operon and increases the affinity of RNA polymerase, thus accelerating transcription; when glucose levels decrease, 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

Question 13

What is differential gene expression?

Answer 13

The expression of different genes by cells with the same genome, giving rise to differences between cell types

• Almost all cells in an organism are genetically identical
• Abnormalities in gene expression can lead to cancer

Question 14

Discuss the regulation of chromatin structure.

Answer 14

• 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

Question 15

What is histone acetylation?

Answer 15

Acetyl groups (-COCH3) are attached to positively charged lysines in histone tails; this looses the 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 loose chromatin

Question 16

What is DNA methylation?

Answer 16

The addition of methyl groups to certain bases in DNA, is associated with reduced transcription in some species; can cause long term inactivation of genes in cellular differentiation

*In genomic imprinting, methylation regulations expression of either the maternal or paternal alleles of certain genes at the start of development

Question 17

What is epigenetic inheritance?

Answer 17

Inheritance of traits transmitted by mechanisms not involving the nucleotide sequence itself

Question 18

What are control elements?

Answer 18

Associated with most eukaryotic genes; segments of noncoding DNA that serve as binding sites for the proteins called transcription factors, which in turn regulate transcription

Control elements and the transcription factors they bind are critical to the precise regulation of gene expression in different cell types

Question 19

What does eukaryotic RNA polymerase require to initiate transcription?

Answer 19

The assistance of transcription factors

Question 20

What are general transcription factors?

Answer 20

Essential for the transcription of all protein-coding genes

Question 21

What are enhancers?

Answer 21

Distal control elements, groupings of which are called enhancers, may be far away from a gene or even located in an intron

*The rate of gene expression can be strongly increased or decreased by the binding of specific transcription factors, either activators or repressors, to the control elements of enhancers

Question 22

In more detail, what is an activator?

Answer 22

A protein that binds to an enhancer and stimulates the 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

Question 23

What can sometimes function as a repressor, inhibiting expression of a particular gene?

Answer 23

Some transcription factors function as repressors; some activators and repressors act indirectly by influencing chromatin structure to promote or silence transcription

Question 24

What is alternative RNA splicing?

Answer 24

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

Question 25

Discuss “Initiation of Translation and mRNA Degradation”

Answer 25

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

Question 26

Discuss “Protein Processing and Degradation”.

Answer 26

After translation, various types of protein processing, including cleavage and the addition of 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

Question 27

Discuss how noncoding RNAs play multiple roles in controlling gene expression.

Answer 27

ncRNAs; 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 at two points: mRNA translation and chromatin configuration

ncRNAs are responsible for X chromosome inactivation, which, in most female mammals, prevents expression of genes located on one of the X chromosomes

Question 28

What are microRNAs?

Answer 28

miRNAs; capable of binding to complementary sequences in mRNA molecules

A single stranded RNA of about 22 nucleotides that forms a complex with one or more proteins; the miRNA allows the complex to bind to any mRNA molecule with at least 7 or 8 nucleotides of complementary sequence

The miRNA complex then either degrades the target mRNA or blocks its translation

It is estimated that expression of at least half of all human genes may be regulated by miRNAs

Question 29

What are small interfering RNAs?

Answer 29

siRNAS; similar to miRNAs in size and function, associating with similar proteins and producing similar results

Turn of expression of genes with related sequences

Question 30

What is RNA interference?

Answer 30

RNAi; the blocking of gene expression by siRNAs; used in the laboratory as a means of disabling specific genes to investigate their function

Question 31

What are piRNAs?

Answer 31

Piwi-interacting RNAs (piRNAs); a newly discovered class of small ncRNAS that induce formation of heterochromatin, blocking expression of some parasitic DNA elements in the genome known as transposons

Question 32

What is differentiation?

Answer 32

The process by which cells become specialized in structure and function

The process by which a cell attains its determined fate

Differentiated cells are specialists at making tissue specific proteins

Question 33

What is morphogenesis?

Answer 33

The physical processes that give an organism its shape constitute morphogenesis, the development of the form of an organism and its structures

Question 34

What is the three step program of differential gene expression that leads to a multicellular organism?

Answer 34

1. Cell division
2. Cell differentiation
3. Morphogenesis

Materials placed into the egg by the mother set up a sequential program of gene regulation that is carried out as cells divide, and this program coordinates cell differentiation during embryonic development

Question 35

What are cytoplasmic determinants?

Answer 35

Maternal substances in the egg that influence the course of early development; after fertilization, early mitotic divisions distribute the zygote’s cytoplasm into separate cells; the nuclei of these cells may thus be exposed to different cytoplasmic determinants, depending on which portions of the zygotic cytoplasm a cell received

The combination of cytoplasmic determinants in a cell helps determine its developmental fate by regulating expression of the cell’s genes during he course of cell differentiation

Question 36

What is induction?

Answer 36

Most influential are the signals impinging on an embryonic cell from other embryonic cells in the vicinity, including contact with cell-surface molecules on neighboring cells and the binding of growth factors secreted by neighboring cells

Such signals cause changes in the target cells, a process called induction

The molecules conveying these signals within the target cell are cell surface receptors and other signaling pathways proteins

The signaling molecules send a cell down a specific developmental path by causing changes in its gene expression that eventually result in observable cellular changes

Question 37

What is determination?

Answer 37

Refers to the point at which an embryonic cell is irreversibly committed to becoming a particular cell type

Once a cell has undergone determination, an embryonic cell can be experimentally placed in another location in the embryo and it will still differentiate into the cell type that is its normal fate

Question 38

What is myoD?

Answer 38

A master regulatory gene; this gene encodes MyoD protein, a transcription factor that binds to specific control elements in the enhancers of various target genes and stimulates their expression

Question 39

What is the body plan?

Answer 39

The organism’s overall three dimensional arrangement; must be established and super imposed on the differentiation process

Question 40

What is pattern formation?

Answer 40

Cytoplasmic determinants and inductive signals both contribute to the development of a spatial organization in which the tissues and organs of an organism are all in their characteristic places

Question 41

What is positional information?

Answer 41

The molecular cues that control pattern formation; provided by cytoplasmic determinants and inductive signals; these cues tell a cell its location relative to the body axes and to neighboring cells and determine how the cell and its progeny will respond to future molecular signals

Question 42

What are homeotic genes?

Answer 42

Control pattern formation in the late embryo, larva, and adult

Question 43

What are embryonic lethals?

Answer 43

Mutations with phenotypes causing death at the embryonic or larval stage

Question 44

What is a maternal effect gene?

Answer 44

A gene that, when mutant in the mothers, results in a mutant phenotype in the offspring, regardless of the offspring’s own genotype

Also called egg polarity genes; one group of these genes sets up the anterior posterior axis of the embryo, while a second group establishes the dorsal ventral axis

*Mutations in maternal effect genes are generally embryonic lethals

Question 45

What are morphogens?

Answer 45

The morphogen gradient hypothesis is where gradients of substances called morphogens establish and embryo’s axes and other features of its form

Question 46

What does cancer result from?

Answer 46

Genetic changes that affect cell cycle control; cancer can be caused by mutations to genes that regulate cell growth and division and mutations in the genes can be caused by spontaneous mutations or environmental influences such as chemicals, radiation, and some viruses

The gene regulation systems that go wrong during cancer are the very same systems involved in embryonic development

Question 47

What are oncogenes?

Answer 47

Cancer causing genes in certain types of viruses

Question 48

What are proto-oncogenes?

Answer 48

The normal versions of the cellular genes that code for proteins that stimulate normal cell growth and division

Question 49

How might a proto-oncogene become an oncogene?

Answer 49

An oncogene arises from a genetic change that leads to an increase either in the amount of the proto-oncogene’s protein product or in the intrinsic activity of each protein molecule. The genetic changes that convert proto-oncogenes to oncogenes fall into three main categories;

1. Translocation or transposition - movement of DNA within the genome; gene moved to new locus, and under new controls (normal growth stimulating protein in excess)
2. Gene amplification - amplification of a proto-oncogene (multiple copies) (normal growth stimulating protein in excess)
3. Point mutation - point mutations in a control element or in the proto-oncogene itself; cause an increase in gene expression (normal growth stimulating protein in excess) (hyperactive or degradation resistant protein)

Question 50

What are tumor suppressor genes?

Answer 50

Inhibit cell division; the proteins they encode help prevent uncontrolled cell growth

Mutations that decrease protein products of tumor-suppressor genes may contribute to cancer onset

Question 51

What are three functions of tumor-suppressor proteins?

Answer 51

Repair damaged DNA
Control cell adhesion
Act in cell-signaling pathways that inhibit the cell cycle

Question 52

What mutations on what genes are common in human cancer?

Answer 52

Mutations in the ras proto-oncogene and p53 tumor-suppressor gene are common in human cancers

Question 53

What is the ras gene?

Answer 53

A G protein that relays a signal from a growth factor receptor on the plasma membrane to a cascade of protein kinases; the cellular response at the end of the pathway is the synthesis of a protein that stimulates the cell cycle

Mutations in the ras gene can lead to production of a hyperactive Ras protein and increased cell division

Question 54

What is the p53 gene?

Answer 54

A tumor-suppressor gene; the protein it encodes is a specific transcription factor that promotes the synthesis of cell cycle inhibiting proteins (prevents a cell from passing on mutations due to DNA damage)

• Activates expression of a group of miRNAs, which in turn inhibit the cell cycle
• Can turn on genes directly involved in DNA repair
• When DNA damage is irreparable, p52 activates “suicide” genes, whose protein products bring about programmed cell death (apoptosis)

A mutation that knocks out the p53 gene, can lead to excessive cell growth and cancer

*The guardian angel of the genome

Question 55

Discuss the multistep model of cancer development.

Answer 55

• Multiple mutations are generally needed for full-fledged cancer; thus the incidence increases with age
• At the DNA level, a cancerous cell is usually characterized by at least one active oncogene and the mutation of several tumor-suppressor genes
• Breast cancer is a heterogeneous disease that is the commonest form of cancer in women in the United States
• A genomics approach to profiling breast tumors has identified four major types of breast cancer

Question 56

Discuss inherited predisposition and environmental factors contributing to cancer.

Answer 56

• Individuals can inherit oncogenes or mutant alleles of tumor-suppressor genes
• Inherited mutations in the tumor-suppressor gene adenomatous polyposis coliare common in individuals with colorectal cancer
• Mutations in the BRCA1or BRCA2gene are found in at least half of inherited breast cancers, and tests using DNA sequencing can detect these mutations

Question 57

Discuss the role of viruses in cancer.

Answer 57

• 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 ofa cell
• Viruses are powerful biological agents

Question 58

What is heterochromatin?

Answer 58

Eukaryotic chromatin that remains highly compacted during interphase and is generally not transcribed

Question 59

What is euchromatin?

Answer 59

The less condensed form of eukaryotic chromatin that is available for transcription