Chapters 15 – 17

Regulation of Gene Expression

Development, Stem Cells, and

Cancer

Viruses

Purpose of Gene Regulation

• Unicellular (bacteria, protists)▫ Prevents waste of cell’s resources creating

unnecessary proteins• Multicellular

▫ Allows for cell differentiation All cells have identical genome, yet express different

portions of it Different cells perform different functions

• Works with feedback inhibition

Operons

• Found in unicellular organisms• “On-Off switch” for genes w/related functions• Components

▫ Operator Region of DNA where repressor protein binds

▫ Controlled genes▫ Regulatory gene (and its product – repressor

protein) Always expressed in cell

lac Operon

• Classic example of operon function• Involves genes associated with lactose digestion

Eukaryotic Gene Regulation

• Regulation occurs at multiple points▫ In the nucleus:

Chromatin modification Protein synthesis RNA processing

▫ In the cytoplasm: RNA transcription Protein processing

In the Nucleus …

• Chromatin modification▫ Histone acetylation

Acetyl group (–COCH3) added to histone proteins DNA packaged more loosely, promoting transcription

▫ DNA methylation Methyl group (–CH3) added to bases – usually cytosine

Prevents protein interaction with that region of chromatin

▫ Alternative RNA splicing

In the Cytoplasm…

Embryonic Development

• Zygote to adult involves cell division, cell differentiation and morphogenesis▫ Cell division increases number of cells▫ Cell differentiation results in different types of

cells▫ Morphogenesis produces new structures

(shaping)

Stem Cells

• Stem cells are unspecialized cells that can reproduce indefinitely (no Hayflick limit) and can differentiate into specialized cells of one or more types▫ Totipotent – exist only early on after fertilization;

can become ANY cell type▫ Pluripotent– descendants of totipotent; can

become any cell derived from the three germ layers

▫ Multipotent– can result in any cell type belonging to a family of cells

Abnormal Regulation of Genes

• Faulty gene expression regulation can lead to cancer

• Research has lead to the discovery of cancer causing genes: oncogenes▫ Oncogenes can arise from a change to a normally-

functioning gene or from certain types of viruses Proto-oncogenes are NORMAL genes that are

involved with NORMAL cell growth and division Ex. Tumor-supressor genes code for proteins that curb

uncontrolled cell growth▫ Over HALF of all human tumors are the result of damage to the

p53 gene Viruses play a role in about 15% of human cancers

Viral Structure

• Viruses are obligate, intracellular parasites▫ Must infiltrate a cell and utilize it’s resources and

machinery to complete viral “life cycle”▫ Infectious agent made of little more than a protein

coat and nucleic acid Capsid – protein coat surrounding genetic material

▫ Bacteriophages (or phages) are viruses that infect bacteria

▫ Most viruses are limited to a specific host or set of hosts they can infect – host range

Typical Viral Life Cycle

Phage Replication

• After infecting a bacterium, phage genetic material may become incorporated into the bacterial chromosome▫ The lysogenic cycle often doesn’t harm the

bacterium▫ Integrated viral DNA known as a prophage

Viral DNA is replicated and passed to daughter cells▫ Changes to environmental conditions may trigger

switch to lytic cycle• Lytic cycle involves replication of viral particles

and assembly of new phages▫ Typically results in rupture (and death) of cell

Animal Viruses

• A greater diversity of viruses exist that infect animals▫ Type of genetic material▫ Outer covering

• Retroviruses utilize RNA as genetic material▫ Carry reverse transcriptase to produce DNA

from RNA▫ Viral genome incorporated into host’s DNA –

provirus Permanent resident of host cell

Unlike phages, cell typically isn’t ruptured during viral production

Vaccines

• Vaccines are derivatives of pathogens that stimulate the immune system▫ Current vaccines CANNOT cause the illness they

vaccinate against Efficacy often decreases with time

▫ Anti-virals can treat viral infections after they’re contracted … not a cure Antibiotics have NO EFFECT on viral infections

Antibiotics combat bacterial infections