Advanced Gene Regulation

MLS-M 430

Course Description

Goals

  1. To attain an advanced understanding of how genes work, including DNA and nucleosome structure, organization of chromatin within chromosomes, and gene regulation in a chromosomal context.
  2. To understand the functions of RNA polymerases and general transcription factors required for RNA synthesis in prokaryotes and eukaryotes.
  3. To understand experimental methods that are the basis for understanding genes and their regulation.
  4. To develop an understanding of how histone chemical modifications, and the proteins that generate and interpret these marks, to achieve so-called epigenetic regulation
  5. To learn to make use of primary literature and recent review articles to explore new fields.

Lectures- two class meetings per week, 75 minutes each

Class meeting

  1. Course overview; DNA structure and chromatin organization
  2. Coding and noncoding RNAs; RNA Polymerases and transcription
  3. Bacterial genes:consensus sequences; RNA polymerase and sigma factors
  4. Bacterial gene regulation I: operons and regulons; activators and repressors
  5. Bacterial gene regulation II: termination and anti-termination; attenuation, riboswitches
  6. Archaeal and Eukaryotic RNA polymerases, archaeal origins of nuclear transcription
  7. Transcription by RNA Polymerase I (Pol I): transcription factors; enhancer function
  8. Transcription by Pol III: different transcription factors for tRNA, 5S RNA and U6 RNA
  9. Transcription by Pol II: mRNA gene organization, modularity of promoters, enhancers

Mid-term exam

  1. Pol II general transcription factors; gene activation; roles of Mediator; activator proteins
  2. Transcriptional activation and enhancer function in the context of chromatin
  3. Regulation of Pol II transcriptional elongation and pausing; the CTD code
  4. mRNA processing; capping, polyadenylation, intron splicing
  5. Alternative mRNA splicing; RNA editing
  6. Transcription termination mechanisms for Pols I, II and III
  7. Transcription in the context of chromatin; chromatin remodeling ATPases
  8. Chemical modification of DNA and histones; chromatin marks of active versus silenced genes
  9. Enzymes and protein complexes that "write" or "read" epigenetic information

Mid-term exam

  1. Epigenomics: genome-wide analyses of chromatin modifications and gene expression states
  2. Euchromatin and heterochromatin; Position effect variegation
  3. Genome defense by gene silencing: transposable elements, retroviruses
  4. Post-transcriptional gene silencing; discovery and functions of microRNAs (miRNAs)
  5. RNA interference; discovery of short interfering RNAs (siRNAs)
  6. RNA-directed histone modification and DNA methylation; transcriptional gene silencing
  7. Epigenetic phenomena; epigenetics of cancer and disease
  8. Long non-coding RNAs
  9. Genome editing using engineered zinc fingers, TALENs, CRISPR/Cas9

Final exam

Reading material

  1. Review articles and primary journal articles provided online (class website)
  2. Reference Textbook: “Lewin’s Genes XI”; Krebs, Goldstein and Kilpatrick, ISBN-13 9781449659851, 2012