Eukaryotic Regulation

Genomic Equivalence Every nucleated cell in an organism has exactly the same DNA as every other nucleated cell in the organism. Implications Ÿ The different cells in an organism create different enzymes and proteins because of Genetic Regulation, not because of a different constitution. Ÿ Because every cell has the same DNA, it is theoretically possible to clone an organism from a single cell. Ÿ The different genes that are used during development are not lost from the cell, merely turned off. Levels of Eukaryotic Regulation

Levels for the control of gene expression goes from chromosomal control to transcriptional control to translational control 1. Regulation of Transcription 1A. Activation of Gene Structure Ÿ Euchromatin vs. Heterochromatin Ÿ DNA Changes w Base modification ü methylation patterns w Amplification and diminution ü extrachromosomal copies of DNA (rRNA in Xenopus) ü tandem copies of DNA (rRNA in Humans) w Transposition ü e.g., mating type ( a vs. a ) w Splicing ü Immunoglobulins 1B. Regulation of Transcription Ÿ Positive control (Regulation at the Enhancer Region using Transcription Factores) Levels of Eukaryotic Regulation

2. Regulation of Splicing (RNA Processing) Ÿ Splicing and transcript stability ü Class Switching 3. Regulation of Transport (mRNA to the cytoplasm) 4. Degradation of mRNA Ÿ mRNA stability 5. Translational Regulation Ÿ Masked or untranslated mRNAs mRNAs that do no translate by some enzymatic reaction masking the ribosome binding site. Ÿ mRNA codons -- Use of wobble to allow mRNAs with different characteristics Some codons are more efficient (or numerous) than others. This allows for some proteins to be translated slow or fast depending on the specific codons they use. Ÿ Stability of mRNAs Some mRNAs are more stable than others and are therefore translated more before they degrade. Related to specific sequence and to the length of the poly-A tail. Levels of Eukaryotic Regulation

6. Posttranslational Regulation (Activity of Protein) Ÿ Polyproteins Gets around one transcript/one cistron limitation by dividing primary polypeptide chain into parts after translation. We can regulate this by the rate of processing. Ÿ Activation Control of rate of activation of enzymes. Enzymes are nonfunctional until activated. Ÿ Inhibition Masking or destroying active enzymes to reduce their function. Ÿ Stability of proteins Some proteins age more quickly than others -- related to their amino acid sequence, even in portions of the protein which are enzymatically inert. Development & Differentiation

1. Gene Activity During Development Ÿ Globin genes Ÿ Polytene chromsomes and chromosome puffs 2. Immunogenetics Ÿ Exception to Genomic Equivalence -- Loss of DNA to developed B cell DNA Ÿ Differential RNA splicing to produce different gene products 3. Drosophila Development Ÿ Embryonic Development Ÿ Imaginal Discs Ÿ Homeotic Genes Development Some Terms

Developmental Fate At some point in the development of an organism, a group of cells (and all the cells descended from them) are destined to become some single structure. At this time, their Developmental Fate is determined. Transdetermination When groups of cells have their developmental fate changed. For example, cells that were destined to become eyes are transdetermined to become wings. Imaginal Discs Thickening of the epidermis in Drosophila and other holometabolous insects. During pupation, the imaginal discs give rise to the adult organs & structures. Drosophila Development

Developmental Stages Ÿ Egg Ÿ Instars Ÿ Pupa Ÿ Adult Developmental Genes

Ÿ Maternal Genes (e.g., Bicoid Protein)

Ÿ Segmentation Genes (e.g., gap, pair-rule, or polarity genes). w Affects the number of segments or the polarity of the segments. Ÿ Homeotic Genes w Affect segment identity w 70% - 90% Homology between Drosophila & Humans. w Short (180 pb) w Homology with DNA-binding proteins