Chapter 18 Gene Expression

I) What are Genes? A) Sequences of nucleotides that determine the sequence of amino acids in proteins B) Two Types of Genes Regulatory Genes Structural Genes

I) What are Genes? A) Sequences of nucleotides that determine the sequence of amino acids in proteins B) Two Types of Genes Regulatory Genes Structural Genes Control transcription and expression of other genes

I) What are Genes? A) Sequences of nucleotides that determine the sequence of amino acids in proteins B) Two Types of Genes Regulatory Genes Structural Genes Control transcription and expression of other genes Function as “on/off” switches

I) What are Genes? A) Sequences of nucleotides that determine the sequence of amino acids in proteins B) Two Types of Genes Regulatory Genes Structural Genes Control transcription and expression of other genes Function as “on/off” switches Some code for RNA

I) What are Genes? A) Sequences of nucleotides that determine the sequence of amino acids in proteins B) Two Types of Genes Regulatory Genes Structural Genes Control transcription and expression of other genes Function as “on/off” switches Some code for RNA Determine the structure of a protein

I) What are Genes? A) Sequences of nucleotides that determine the sequence of amino acids in proteins B) Two Types of Genes Regulatory Genes Structural Genes Control transcription and expression of other genes Function as “on/off” switches Some code for RNA Determine the structure of a protein Control amino acid sequences

I) Differentiation The process in which cells become specialized as specific genes are activated Function of a cell is dictated by DNA Not all genes are activated in every cell Some genes are only active at specific points in the life cycle of a cell

III) Prokaryotic Gene Regulation OPERONS - Specific genes within DNA that control the transcription of RNA and control protein synthesis Operons contain four components Regulatory Gene – codes for either a repressor protein or an activator protein Repressor protein prevents RNA transcription (turns genes off) Activator protein starts RNA transcription (turns genes on) Promoter – region of DNA where RNA polymerase binds and begins transcription (the Start Codon) Operator – region of DNA to which a repressor or activator protein binds – this is the “ON/OFF SWITCH” Structural Gene – DNA sequences that determine the amino acid sequence for a specific protein or proteins

Inducible Genes Repressible Genes Genes that are usually off and need to be activated for short periods of time

Inducible Genes Repressible Genes Genes that are usually off and need to be activated for short periods of time Require an activator to remove a repressor protein

Inducible Genes Repressible Genes Genes that are usually off and need to be activated for short periods of time Require an activator to remove a repressor protein lac operon

Inducible Genes Repressible Genes Genes that are usually off and need to be activated for short periods of time Require an activator to remove a repressor protein lac operon Genes that are usually on all the time and need to be inactivated for brief periods

Inducible Genes Repressible Genes Genes that are usually off and need to be activated for short periods of time Require an activator to remove a repressor protein lac operon Genes that are usually on all the time and need to be inactivated for brief periods Require a repressor to block transcription

Inducible Genes Repressible Genes Genes that are usually off and need to be activated for short periods of time Require an activator to remove a repressor protein lac operon Genes that are usually on all the time and need to be inactivated for brief periods Require a repressor to block transcription trp operon

IV) Eukaryotic Gene Regulation A) Control of Transcription 1) Transcription Activation Transcription Factors Proteins that bind to promoters and affect RNA polymerase activity Coactivator proteins then bind to the transcription factors (the activators) and helps initiate RNA transcription These enhance or promote transcription Inhibition of Transcription Methylation Methyl groups (-CH3) attach themselves to the cytosines that reside in CG (cytosine-guanine) doublets on DNA. Methylation near a gene promoter on DNA will generally prevent transcription of that gene.

Factor Promoter Transcription Estrogen receptors normally reside in the cell’s nucleus, along with DNA molecules. In the absence of estrogen molecules, these estrogen receptors are inactive and have no influence on DNA (which contains the cell’s genes). But when an estrogen molecule enters a cell and passes into the nucleus, the estrogen binds to its receptor, thereby causing the shape of the receptor to change. This estrogen-receptor complex then binds to specific DNA sites, called estrogen response elements, which are located near genes that are controlled by estrogen. After it has become attached to estrogen response elements in DNA, this estrogen-receptor complex binds to coactivator proteins and more nearby genes become active. The active genes produce molecules of messenger RNA, which guide the synthesis of specific proteins. These proteins can then influence cell behavior in different ways, depending on the cell type involved.

Regulatory Switches and Gene Regulation

Small RNAs such as miRNAs and siRNAs block RNA translation a) miRNA: B) Post-transcriptional Control in Eukaryotes 1) Gene regulation after RNA transcription 2) RNA interference (RNAi) Small RNAs such as miRNAs and siRNAs block RNA translation a) miRNA: microRNAs (miRNAs) are a class of naturally occurring, small non-coding RNA molecules, about 21–25 nucleotides in length. miRNAs are partially complementary to one or more messenger RNA (mRNA) molecules, and their main function is to down-regulate (supress) gene expression miRNA forms double stranded RNA to prevent translation into protein miRNA base pairing is not exact – results in many more possible points of interference

siRNA (small interfering RNA) Double Stranded (dsRNA) is cleaved by an enzyme, Dicer, into double stranded small interfering RNAs (siRNA) the siRNAs become integrated into a multi-subunit protein complex, commonly known as the RNAi induced silencing complex (RISC), which guides the siRNAs to the target RNA sequence At some point the siRNA and RISC directs degradation of the complementary mRNA sequence Many genes are thought to be regulated this way Prevents RNA translation into protein siRNA has exact base pairing

EPIGENETICS Gene expression regulated by environmental factors. Changes do not involve nucleotide sequence changes. Changes can be passed to future generations. Diet, stress, and other factors play a role. Epigenetics is regulated by DNA methylation Methylation inhibits gene expression while demethylation induces gene expression

Effects of Bis-Phenol A (BPA) BPA causes demethylation which activates genes known to induce obesity in GENETICALLY IDENTICAL MICE BPA is linked to diabetes, obesity, and developmental problems in children BPA is an estrogen-like substance that affects cell growth and differentiation. Effects of BPA can be seen in fourth generation offspring

When pregnant yellow agouti mothers were fed BPA, more yellow, unhealthy babies were born than normal. Exposure to BPA during early development had caused decreased methylation of the agouti gene. However, when BPA-exposed, pregnant yellow mice were fed methyl-rich foods, the offspring were predominantly brown. The maternal nutrient supplementation had counteracted the negative effects of exposure

Lick Your Rats! The nurturing behavior of a mother rat during the first week of life shapes her pups' epigenomes. The epigenetic pattern that mom establishes tends to stay put, even after the pups become adults. These patterns can be reversed through the introduction of methyl in the diet or a removal of methyl using chemical compounds

BARR BODIES A Barr body (named after discoverer Murray Barr) is the inactive X chromosome in a female somatic cell. A normal human female has only one barr body per somatic cell, while a normal human male has none.