Chapter 17: Regulation of Gene Expression in Eukaryotes Summary (page 1)Started at 1:15pm- Gene expression in Eukaryotes is tightly controlled in order to express the required levels of gene products at specific timeso Eukaryotic genes contain histones and other proteins to form highly compact chromatin structures and must modify this structural organization in for to influence gene expressiono mRNAs must be spliced, capped, and polyadenylated prior to transport from the nucleuso Eukaryotic genes are located on many chromosomes (rather than just one) and these chromosomes are enclosed within a double-membrane-bound nucleuso mRNAs have a wide range of half-lives whereas prokaryotic mRNAs decay very rapidly in response to environmental changeso translation rates, the way proteins are processed, modified, and degraded can be modulated- Chromatin Remodeling: expression has to be altered to turn on/off genes, critical to gene expression, chromatin has to loosen up in order for transcription to starto SWI/SNF= chromatin remodelers, move chromatin around- Interchromosal Domain: where transcription occurs- Acteylation: acts on histone around promoter region, eliminating charge, letting polymerase in to start translation- Deacetylation: “closed,” genes cannot be transcribed Both have a big role in cancer (abnormal level of gene expression)- Histone code: cells constantly modify histoneso HAT: histone acetyl transferase- DNA Methylation: major way of remolding, adding methyl group to DNA, CG-> small fraction of C’s are methylated, shutting off transcriptiono Shuts things down, if gene is heavily methylated then the gene expression is reducedo Azactosine (cytosine methylated, where one C-H bond changes to N) induces demethylation, doing that can turn on certain genes (cancer), turns up gene expression of genes that have been turned off by methylation o Too low of levels are common in cancer cells (global hypomethylation) or in certain placesof cancer (selective hypermethylation)o Tumor suppressor genes protect against cancer, hypermethylated, reversibleo IF the genome loaded with transposable elements, many get methylated (keeping them atbay) but can possibly become active leading to instability- Epigenetics: describes the things you can do to the DNA to change gene expressiono Stable/ heritable gene expressiono Without changing sequenceo Epigenators: environmental stress can activate signal transduction to intitator to either activate or silence genes Maintainers of these changes are DNA methylases, histone acetlyases, and histone deacetylaseso- Programmed DNA Rearrangements Regulate expression of a small number of geneso Antigen recognition protects organisms against infections and the presence of foreign substances that may enter blood or by tissues by recognizing molecules on the surface of these foreign substances and by physically binding them in a lock-and-key configuration Antigens are molecules, usually proteins, which bring about an immune responseo Humoral immunity involves the production of proteins called immunoglobulins (antibodies)that bind directly to antigensChapter 17: Regulation of Gene Expression in Eukaryotes Summary (page 2) Immunoglobulins are synthesized by a type of blood cell: B lymphocyte (B cell) which are developed and matured in the bone marrow- Eukaryotic transcription initiation is regulated by specific cis-acting siteso Promoter region recognizes the transcript machinery and binds one or more proteins that regulate transcription for initiation Core promoter determines the accurate initiation of transcription by RNA poly II Proximal promoter elements modulate the efficiency of basal levels of transcription Focused: specify transcription initiation at single specific nucleotide (transcriptionstart site), associated with highly regulated genes Dispersed: direct initiation at a number of weak transcription start sites, associated with genes that are transcribed constitutively Enhancers: located on either side of a gene, away from the gene, or within a gene; achieve the maximum level of transcription; responsible for time- and tissue-specific gene expression; cis regulator- Different from promoter because:o Position of enhancer need not be fixed relative to the gene it regulateso Orientation of an enhancer can be inverted without significant effect on its actiono If enhancer is experimentally moved adjacent to a gene elsewhere or if unrelated gene is placed near an enhancer, thenewly adjacent gene is enhanced Silencer: cis regulator also, acts upon eukaryotic genes to repress the level of transcription initiation  Insulator: when want gene on at high levels, it prevents the spred of remodeling, turning on gene off but doesn't interfere with another- Eukaryotic transcription initiation is regulated by transcription factors that bind to cis-acting siteso Transcription factors are regulatory proteins that have diverse and complicated effects on transcription; they interact with cis regulating elements Activators increase the levels of transcription initiation Repressors reduce transcription levelso DNA Binding domain: binds to specific DNA sequences present in the cis-acting regulatory site Helix-turn-helix: presence of two sigma helices sepearated by a “turn: of serval amino acids enables the protein to bind to DNA Zinc finger: clusters bind to zinc atoms, fold into loops, and interact with specific DNA sequences Basic Leucine Zipper: when two bZIP-containing molecules dimerize, the leucine residues “zip” togethero Trans-activation/ trans-repression domain: activated or repressed transcription - Activators and Repressors interact with General transcription factors at the promotero General transcription factors are need to initate either basal-lebel or enhanced levels of transcriptiono Pre-initiation complex provides a platform for RNA poly II to bind to a promotor and initiatetranscriptiono TATA Box: polymerase II binds Enhancer makes enhancesome bridge to TATA box and polymerases proteinso Elongation complex process that occurs when RNA poly clears the promoter and proceeds down the DNA templateChapter 17: Regulation of Gene Expression in Eukaryotes Summary (page 3)o Formation of a DNA loop allows factors that bind to an enhancer or silencer at a distance from a promoter to interact with general transcription factors in the pre-initiation complex and to regulate the level of transcriptiono Ways in