BIOL-L211 Lecture 24 Outline of Last Lecture I. Activating Domains and DNA-binding DomainsII. Modification of N-terminal Histone TailsIII. ArticleOutline of Current Lecture I. Article (cont.)II. Activators, Repressors, and SynergismIII. EpigeneticsCurrent LectureTranscriptional Regulation in Eukaryotes and EpigeneticsI. Article (cont.)A. Stickleback fish has two forms1. Deep-water: has spiny pelvic fin underneath2. Shallow-water: lacks pelvic finB. Pitx1 gene controls body structure development1. A separate enhancer controls activity in each tissue2. In shallow-water sticklebacks, there is a mutation in the pelvic enhancerC. Duffy Protein: protein that is sought out by malarial parasites1. Functions in the spleen, brain, kidneys, and most importantly red blood cells2. Duffy gene uses separate enhancersThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.3. Binds to surface of red blood cells- recognized by malarial parasites4. West African populations developing mutation with red blood cell enhancer5. Duffy cannot find the red blood cells -> increased malaria resistanceII. Activators, Repressors, and SynergismA. Synergy: the cooperation between two or more parts to produce an effect greater than the sum of the parts1. Ex: Recruitment of mediator complex by two activators2. Together, the activators are able to recruit the mediator complexB. Cooperative Binding of Activators1. When the binding of one protein to a specific DNA binding site helps another protein to bind to a nearby siteC. Examples: Protein A binds DNA and helps Protein B bind DNA1. A and B directly interact ("Classical" example)2. A and B indirectly interact (both interact with Protein X)3. Protein A recruits nucleosome remodeler (which uncovers binding site for B)4. Protein A binds DNA that is associated with the nucleosome (DNA unwinds and exposes binding site for B)D. Transcriptional Repressors1. Bind DNA and repress transcription2. DO NOT bind a site overlapping promoter (usually)3. Transcriptional repressors NOT associated with genes turning off4. Methods:a. Repressor (R) binds the site overlapping activator (A) binding siteb. R interacts with and thus blocks activator's activating domainc. R interacts with the preinitiation complex and inhibits the initiation of transcriptiond. Histone modifiers recruited by repressorIII. EpigeneticsA. DNA modifications can cause transcriptional "silencing"B. DNA methylase: enzyme that methylates DNA1. NOT a mutation2. Inhibits protein binding3. Recruits histone modifiers4. Sometimes despite physical blocking, transcriptional machinery still proceeds (Leaky Transcription)C. Methylation of histones causes condensingD. Histone Methyl Transferase (HMT): adds a methyl group to histones1. Can have varied substrate specificity and number of methyl groupsE. Histone Demethylases (HDM): Removes methyl groupsF. Epigenetics: regulation of gene expression by chemical modification of histones or DNA1. Can be inherited in the absence of the signal that initiated the modificationG. Maintenance Methylase: recognizes hemimethylated DNA1. Methylates unmethylated strand2. Methylation pattern
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