 2.e.1 – Timing and coordination of specific events are necessary for the normal development of an organism, and these events are regulated by a variety of mechanisms ( ).  3.b.1 – Gene regulation results in differential gene expression, leading to cell specialization ( ).  3.b.2 – A variety of intercellular and intracellular signal transmissions mediate gene expression ( ).  4.a.3 – Interactions between external stimuli and regulated gene expression result in specialization of cells, tissues, and organs (18.4).

 Some bacteria can regulate their gene expression based on their surroundings E. coli needs tryptophan to survive; if it isn’t getting trp from its environment (such as the human colon), then it makes its own When the host is ingesting enough trp for the E. coli, the bacteria inhibits enzyme activity thereby shutting down the synthesis of trp and conserving energy.

 Fig. 18.2, page 352  An operon includes the operator (which controls the access of RNA polymerase to the genes), the promoter (a site where RNA polymerase can bind to DNA and begin transcription), and all the genes they control

 Using trp synthesis as an example: The trp operon is turned on meaning that RNA polymerase can bind to the promoter and transcribe the genes of the operon The trp repressor switches the operon off, and the repressor binds to the operator blocking attachment of RNA polymerase to the promoter preventing gene transcription Fig. 18.3, page 353

 3 billion base pairs  ~30,000 genesgenes  Total of almost 3 FEET of DNA in each and every cell in our bodies

 With so much DNA in a cell, how is it organized or packaged?  How is the expression of the DNA controlled?

1. Nucleosomes 2. Chromatin Fibers 3. Looped Domains 4. Chromosomes Focus on #1 & #4

 "Beads on a String”  DNA wound on a protein core  Packaging for DNA  Controls transcription

 Two molecules of four types of Histone proteins  H1- 5th type of Histone protein attaches the DNA to the outside of the core

 Large units of DNA/chromatin/proteins  Appear only during cell division (after Interphase)  Similar to "Chapters" in the Book of Life

1. Heterochromatin - highly condensed chromatin; areas that are not transcribed 2. Euchromatin - less condensed chromatin; areas of active transcription

1. Repetitive Sequences 2. Satellite DNA 3. Interspersed Repetitive DNA 4. Multigene Families

 Give regions of the DNA different densities  Linked to some genetic disorders. Ex. - Fragile X Syndrome Huntington’s disease

 A collection of identical or very similar genes  From a common ancestral gene.  May be clustered or dispersed in the genome

 Identical genes for the same protein Ex: Ribosomal Protein and rRNA  Result - Many copies of ribosomes possible  Most common gene in DNA

 Related clusters of genes that are nearly identical in their base sequences.  Ex: Globin Genes

 Gene with sequences very similar to real genes, but lack promoter sites  Are not transcribed into proteins  Possible proof of transpositions?

 Changes in the ways a gene can be expressed  Seen only in somatic cells  Have major effects on gene expression within particular cells and tissues

1. Gene Amplification 2. Selective Gene Loss 3. Genomic Rearrangements

 The selective replication of certain genes  Ex: rRNA genes in eggs  Result - many copies of rRNA for making ribosomes

 Loss of genes or chromosomes in some tissues during development  Result - DNA (genes) lost and not expressed

 Shuffling of DNA areas (not from meiosis)  Ex: Transposons retrotransposons antibody genes Examples of Transposons: flower petals

 Complicated Process  Many levels of control are possible  Hint - students should understand several mechanisms of control (see slides to follow)

1. Nucleus - those inside the nuclear membrane 2. Cytoplasm - those that occur in the cytoplasm

1. Extra-Cellular Signals (Chapter 11 – Cell communication) 2. Chromatin Modifications 3. Transcriptional Control 4. Posttranscriptional Control

 DNA Methylation  Histone Acetylation  Gene rearrangements  Gene amplification

 Addition of methyl groups (-CH 3 ) to DNA bases  Result - long-term shut-down of DNA transcription  Ex: Barr bodies

 Attachment of acetyl groups (-COCH 3 ) to AAs in histones  Result - DNA held less tightly to the nucleosomes, more accessible for transcription

 Ex: Enhancers Areas of DNA that increase transcription.  Ex: DNA-Binding Domains Proteins that bind to DNA and regulate transcription  Ex: regulatory RNA. Small RNA molecules that are not translated Usually interact with DNA  Result - genes are more (or less) available for transcription.

1. RNA Processing Ex - introns and exons 2. RNA Transport moving the mRNA into the cytoplasm 3. RNA Degradation breaking down old mRNA

1. Translation 2. Polypeptide Changes

 Regulated by the availability of initiation factors  Availability of tRNAs, AAs and other protein synthesis factors (Review Chapter 17)

 Changes to the protein structure after translation  Ex: Cleavage Modifications Activation Transport Degradation

 Cancer - loss of the genetic control of cell division  Balance between growth-stimulating pathway (accelerator) and growth- inhibiting pathway (brakes)

 Normal genes for cell growth and cell division factors  Genetic changes may turn them into oncogenes (cancer genes)  Ex: Gene Amplification, Translocations, Transpositions, Point Mutations

 Genes that inhibit cell division Ex - p53, p21

 RAS - a G protein  When mutated, causes an increase in cell division by over-stimulating protein kinases  Several mutations known

 p53 - involved with several DNA repair genes and “checking” genes.  When damaged (e.g. cigarette smoke), can’t inhibit cell division or cause damaged cells to apoptose.

 Agents that cause cancer Ex: radiation, chemicals  Most work by altering the DNA, or interfering with control or repair mechanisms  See Chapter 17 for more on this!

 Cancer is the result of several control mechanisms breaking down Ex: Colorectal Cancer requires 4 to 5 mutations before cancer starts

Colorectal Cancer

 Recognize the operon model for gene regulation in prokaryotes.  Identify different mechanisms of eukaryotic gene expression control.  Recognize the roles of RNA in controlling gene expression.  Recognize examples of differential gene expression in multicellular organisms.  Recognize that cancer is caused by changes in gene regulation.