Gene Regulation in Eukaryotes Notes

Overview: Eukaryotic organisms do not want to express all of their genes all of the time, and gene regulation is very complex for them. Differences Between Prokaryotes and Eukaryotes: Prokaryotes: 1. simple, unicellular organisms 2. Gene regulation allows them to respond to their environment. Eukaryotes: 1. complex, multicellular organisms 2. Gene regulation allows cell specialization. The Need for Gene Regulation in Eukaryotes: cell specialization many different cell types each serve a function and activates a different subset of genes Levels of Regulation: A gene is expressed if the protein is produced because it will carry out the function that the gene identified. Production of protein in eukaryotic cells: Transcription RNA Processing AAAAAA AAAAAA mRNA Longevity

AAAAAA Translation Regulation occurs in the levels of transcription, RNA processing, mRNA longevity, and translation.

Regulation of RNA Processing: RNA processing involves adding a 5 cap, 3 poly (A) tail, and removal of introns. Two types of RNA regulation: 1. whether or not an RNA gets processed 2. exons are kept in the mRNA First type: If an RNA is not processed, it will not be translated or transported out of the nucleus. Second type: This type can affect the function of the protein produced. exon shuffling exons that can be exchanged in the process Examples: 1. In mammals, the calcitonin gene produces a hormone in one cell and a neurotransmitter in another cell. 2. In Drosophila, the sex-lethal RNA can produce an mRNA encoding a functional polypeptide or an mRNA with a premature stop codon that encodes a short, nonfunctional polypeptide due to alternate splicing. Regulation of RNA Longevity: If one mRNA molecule lasts for five minutes in the cytoplasm before being degraded, and another mRNA lasts for an hour before being degraded, more of the second polypeptide will be produced if both are translated continually while they exist. The lifespan of the mRNA is decreased if the sequence is present more often 3 UTR location of information for lifespan sequence AUUUA - signal for early degradation

Regulation of Translation: Whether or not an mRNA molecule is translated can be controlled. Example: Many animals confiscate large amounts of mRNA in their eggs, and those mRNA molecules are translated only if the egg is fertilized. Regulation of Transcription: Differences between transcriptional regulation in prokaryotes and eukaryotes: Prokaryotes: 1. Prokaryotic genes are regulated mainly by repressors, Eukaryotes: 1. Eukaryotic genes are not organized into operons. 2. Eukaryotic genes are mainly regulated by transcriptional activators, which are transcription factors. Regulatory Elements of Eukaryotic Genes: enhancers - DNA sequences associated with the gene being regulated, responsible for increasing transcription levels and regulating cell- or tissue-specific transcription, function by being recognized and bound to by transcription factors promoter - responsible for initiating low levels of transcription and determining the transcription start site Tissue-Specific Gene Expression: A gene is turned on in one cell type depends mostly on whether the transcription factor for the gene's enhancer is active or not in a cell. Mechanisms by which transcription factors can be regulated:

1. presence or absence of a transcription factor in a cell factor is present - gene is transcribed factor is not present - gene is not transcribed 2. activity of the gene encoding that transcription factor heat shock genes - encode proteins that help the organism survive heat stress heat shock transcription factor activated only when greatly increased temperatures are detected 3. signals from other cells in the same organism (hormones and growth factors) Two basic mechanisms: 1. steroid hormones - lipid derivatives, can cross the cytoplasmic membrane into a cell, where they bind to their specific receptor 2. steroid receptors - transcription factors, become activated and initiate transcription of a specific set of genes when bind to their ligand peptide hormones - must bind to a receptor on the cell surface, can cause activation of a transcription factor that initiates transcription of a specific set of genes Classes of Specialized Transcription Factors: All specialized transcription factors have two functional domains or regions: DNA-binding domain - recognizes the specific DNA sequence of the enhancer and binds to it transactivation domain - interacts with other proteins and increases the rate of transcription thereby Five basic types of transcription factors:

1. zinc finger proteins have a peptide sequence that includes two cysteines and two histidines at specific locations in the polypeptide, usually found in pairs 2. helix-turn-helix proteins - contain three alpha helices joined by curved stretches of polypeptide sequence homeodomain - most important type of helix-turn-helix motif, DNA binding domain of a family of developmentally important transcription factors 3. leucine zipper proteins - these polypeptides dimerize (join together to form a pair).in order to bind DNA leucine zipper - alpha helix containing a leucine in every other turn of the helix 4. helix-loop-helix proteins - dimerize by their helix-loop-helix domain in order to bind DNA helix-loop-helix domain - consists of two alpha helices joined by a polypeptide loop. 5. 5. 5. steroid receptors - have a third functional domain in addition to the two shared by all transcription factors called a steroid-binding domain