Chapter 17 Regulation of Gene Expression in Eukaryotes Summary page 1 Started at 1 15pm products at specific times Gene expression in Eukaryotes is tightly controlled in order to express the required levels of gene o Eukaryotic genes contain histones and other proteins to form highly compact chromatin structures and must modify this structural organization in for to influence gene expression o mRNAs must be spliced capped and polyadenylated prior to transport from the nucleus o Eukaryotic genes are located on many chromosomes rather than just one and these chromosomes are enclosed within a double membrane bound nucleus o mRNAs have a wide range of half lives whereas prokaryotic mRNAs decay very rapidly in response to environmental changes o 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 start o 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 histones o 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 transcription o Shuts things down if gene is heavily methylated then the gene expression is reduced o 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 places of cancer selective hypermethylation o Tumor suppressor genes protect against cancer hypermethylated reversible o IF the genome loaded with transposable elements many get methylated keeping them at bay but can possibly become active leading to instability Epigenetics describes the things you can do to the DNA to change gene expression o Stable heritable gene expression o Without changing sequence o Epigenators environmental stress can activate signal transduction to intitator to either Maintainers of these changes are DNA methylases histone acetlyases and activate or silence genes histone deacetylases o Programmed DNA Rearrangements Regulate expression of a small number of genes o 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 response o Humoral immunity involves the production of proteins called immunoglobulins antibodies that bind directly to antigens Chapter 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 sites o 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 transcription start 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 o Orientation of an enhancer can be inverted without significant regulates effect on its action o If enhancer is experimentally moved adjacent to a gene elsewhere or if unrelated gene is placed near an enhancer the newly 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 sites o 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 levels o 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 together o Trans activation trans repression domain activated or repressed transcription Activators and Repressors interact with General transcription factors at the promoter o General transcription factors are need to initate either basal lebel or enhanced levels of transcription transcription o Pre initiation complex provides a platform for RNA poly II to bind to a promotor and initiate o TATA Box polymerase II binds Enhancer makes enhancesome bridge to TATA box and polymerases proteins o Elongation complex process that occurs when RNA poly clears the promoter and proceeds down the DNA template Chapter 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 transcription o Ways in which transcription activators and repressors may increase or decrease the rate of transcription initiation They bind to chromatin near a gene s