CONTROL OF GENE EXPRESSION 2012 Pearson Education, Inc.
CONTROL OF GENE EXPRESSION 2012 Pearson Education, Inc. Proteins Interact with DNA to turn Prokaryotic Genes On or Off In Response to Environmental Changes What is the difference between gene regulation and gene expression? E. coli in the gut must regulate genes in order to respond to a changing environment Proteins Interact with DNA to turn Prokaryotic
Genes On or Off In Response to Environmental Changes An operon is a cluster of related genes and their control sequences Mainly in prokaryotes E. coli uses the lactose operon when it encounters lactose so that all enzymes needed for lactose metabolism are expressed at once The lactose (lac) operon includes 1. Three lactose-utilization genes 2. A promoter sequence
3. An operator sequence where a repressor can bind Proteins Interact with DNA to turn Prokaryotic Genes On or Off In Response to Environmental Changes Regulation of the lac Operon It is regulated by a regulatory gene which codes for a repressor protein the regulatory gene is not a part of the operon and is always transcribed & translated When lactose is absent: the repressor protein binds the operator preventing transcription When lactose is present: lactose inactivates the repressor protein so, operator is unblocked and RNA pol. can bind the promoter so all three genes of operon are transcribed
Operon turned off (lactose is absent): Regulatory gene Promoter Operator OPERON Lactose-utilization genes DNA RNA polymerase cannot attach to the promoter mRNA Protein
Active repressor Operon turned on (lactose inactivates the repressor): DNA RNA polymerase is bound to the promoter mRNA Translation Protein Lactose Inactive
repressor Enzymes for lactose utilization Multiple Mechanisms Regulate Gene Expression in Eukaryotes Multiple control points exist in Eukaryotic gene expression Genes can be turned on or off, sped up, or slowed down Control points include: 1. Chromosome changes and DNA unpacking 2. Control of transcription 3. Control of RNA processing
cap and tail, RNA splicing 4. Flow through nuclear envelope 5. Breakdown of mRNA 6. Control of translation 7. Control after translation cleavage/modification/activation of proteins protein degradation Chromosome
Chromosome DNA unpacking Other changes to the DNA DNA Gene Gene Transcription Exon RNA transcript Intron Addition of a cap and tail Splicing
mRNA in nucleus Tail Cap Flow through NUCLEUS nuclear envelope CYTOPLASM Figure 11.7_2 mRNA in cytoplasm CYTOPLASM Breakdown of mRNA Brokendown
mRNA Translation Polypeptide Polypeptide Cleavage, modification, activation Active protein Active protein Breakdown of protein Amino acids
Chromosome Structure and Chemical Modifications can Affect Gene Expression DNA packing: Eukaryotic chromosomes undergo multiple levels of folding and coiling DNA double helix (2-nm diameter) Nucleosomes: DNA wrapped around histone proteins Nucleosomes wrap into a tight helical fiber This fiber coils further into a thick supercoil Further compaction of DNA leads to a
metaphase chromosome (30-nm) (300-nm) 700 nm Chromosome Structure and Chemical Modifications can Affect Gene Expression DNA packing can prevent gene expression by preventing RNA polymerase & other proteins from contacting DNA Cells seem to use higher levels of packing for long-term inactivation of genes Highly compacted chromatin is generally not expressed
Chromosome Structure and Chemical Modifications can Affect Gene Expression Epigenetic inheritance Inheritance of traits transmitted by mechanisms that do not alter the sequence of nucleotides in DNA Chemical modification of DNA bases or histone proteins can result in epigenetic inheritance Methylation of DNA prevents its expression Removal of extra methyl groups can turn on some of these genes Chromosome Structure and Chemical Modifications can Affect Gene Expression X-chromosome inactivation In female mammals either the maternal or paternal chromosome is randomly inactivated This occurs early in embryonic development; all cells that
arise from this cell have the same inactivated X chromosome. Ex. Tortoiseshell fur coloration is due to inactivation of X chromosomes in heterozygous female cats. Early Embryo Adult Two cell populations X chromosomes Allele for orange fur Cell division and random
X chromosome Active X inactivation Inactive X Allele for black fur Inactive X Active X Orange fur Black fur Control of Transcription in Eukaryotes Eukaryotes use regulatory proteins called transcription factors to regulate transcription
Transcription factors can be activators or repressors Activator proteins bind DNA sequences called enhancers DNA bending proteins bend DNA to bring bound activators closer to the promoter Bound activators interact with other TFs at the promoter; allowing RNA pol. to transcribe the gene Enhancers Promoter Gene DNA Activator
proteins Transcription factors Other proteins RNA polymerase Bending of DNA Transcription Control of RNA Processing Breakdown of mRNA Enzymes in the cytoplasm destroy mRNA Long-lived mRNAs can be translated into many more protein molecules than short-lived ones
mRNAs of eukaryotes have lifetimes from hours to weeks Regulation of Translation Using MicroRNAs A significant amount of the genome codes for microRNAs RNA interference (RNAi) is the use of miRNA to control gene expression microRNAs (miRNAs) bind complementary sequences on target mRNA leading to degradation of the target mRNA blocking translation of an mRNA miRNAs can be injected into a cell to turn off a specific gene sequence. Protein miRNA 1
Regulation of Gene Expression by Protein Activation S S S S S Folded polypeptide (inactive) S S
Cleavage S S SH SH Initial polypeptide (inactive) SH Folding of the polypeptide and the formation of
SS linkages S SH SH SH Protein Activation- After translation is complete some proteins require alterations before they are fully function S S Active form of insulin
Regulation by Protein Destruction Protein Breakdown Final control mechanism Cells can adjust the kinds and amounts of its proteins in response to environmental changes Damaged proteins are usually broken down right away and replaced CLONING OF PLANTS AND ANIMALS 2012 Pearson Education, Inc. Plant cloning shows that differentiated cells may retain all of their genetic potential Most differentiated cells retain a full set of genes,
even though only a subset may be expressed. Evidence is available from plant cloning, in which a root cell can divide to form an adult plant 2012 Pearson Education, Inc. Root of carrot plant Single cell Root cells cultured in growth medium Cell division in culture
Plantlet Adult plant Nuclear transplantation Can be Used to Clone Animals Animal cloning can be achieved using nuclear transplantation Reproductive cloning is the use of nuclear transplantation to produce new organisms Reproductive cloning is used to produce animals with desirable traits to produce better agricultural products produce therapeutic agents restock populations of endangered animals Donor
cell Nucleus from the donor cell Blastocyst The nucleus is removed from an egg cell. A somatic cell from an adult donor is added. The cell grows in culture to produce an early embryo
(blastocyst). Reproductive cloning Blastocyst The blastocyst is implanted in a surrogate mother. A clone of the donor is born. Therapeutic cloning Embryonic stem cells are removed from the blastocyst and grown
in culture. The stem cells are induced to form specialized cells. Nuclear transplantation Can be Used to Clone Animals A blastocyst made through nuclear transplantation provides embryonic stem (ES) cells. This procedure can be used to produce cell cultures for research stem cells for therapeutic treatments as in therapeutic cloning Stem Cells When grown in laboratory culture, embryonic
stem cells can divide indefinitely can give rise to many types of differentiated cells are more promising than adult stem cells Adult stem cells can give rise to many, but not all, types of cells Blood cells Adult stem cells in bone marrow Nerve cells Cultured embryonic stem cells
Heart muscle cells Different culture conditions Different types of differentiated cells Reproductive Cloning has Valuable Applications, but Human Reproductive Cloning Raises Ethical Issues Since Dollys landmark birth in 1997, researchers have cloned many other mammals, including mice, cats, horses, cows, mules, pigs, rabbits, ferrets, and dogs. Cloned animals can show
differences in anatomy and behavior due to environmental influences random phenomena 2012 Pearson Education, Inc. THE GENETIC BASIS OF CANCER 2012 Pearson Education, Inc. Cancer Results from Mutations in Genes that Control Cell Division Mutations in two types of genes can cause cancer 1. Oncogenes Oncogenes are cancer causing genes produced when a normal proto-oncogene is mutated
Proto-oncogenes are normal genes that code for proteins that affect the cell cycle 2. Tumor-suppressor genes Tumor-suppressor genes normally inhibit cell division or function in the repair of DNA damage Mutations inactivate TS genes and allow uncontrolled division to occur 2012 Pearson Education, Inc. Proto-oncogene (for a protein that stimulates cell division) DNA A mutation within the gene
Multiple copies of the gene Oncogene Hyperactive growthstimulating protein in a normal amount The gene is moved to a new DNA locus, under new controls New promoter Normal growthstimulating protein
in excess Normal growthstimulating protein in excess Tumor-suppressor gene Normal growthinhibiting protein Cell division under control Mutated tumor-suppressor gene Defective,
nonfunctioning protein Cell division not under control An oncogene A tumor-suppressor DNA changes: is activated gene is inactivated A second tumorsuppressor gene is inactivated Cellular Increased changes: cell division 1
Growth of a malignant tumor 3 Colon wall Growth of a polyp 2 Figure 11.17B 1 Chromosomes mutation Normal cell
2 mutations 3 4 mutations mutations Malignant cell Lifestyle Choices Can Reduce the Risk of Cancer After heart disease, cancer is the second-leading cause of death in most industrialized nations Cancer can run in families if an individual inherits an oncogene or mutant allele of a tumor-suppressor gene Most cancers cannot be associated with an
inherited mutation Lifestyle Choices Can Reduce the Risk of Cancer Carcinogens are cancer-causing agents that alter DNA Most mutagens (substances that promote mutations) are carcinogens
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