CH 19: Transcriptional Regulation in Eukaryotes

A. Conserved Mechanisms of Transcriptional Regulation from Yeast to Mammals

B. Recruitment of Protein Complexes to Genes by Eukaryotic Activators

C. Signal Integration and Combinatorial Control

D. Transcriptional Repressors

F. Gene "Silencing" by Modification of Histones and DNA

E. Signal Transduction and the Control of Transcriptional Regulators

G. Epigenetic Gene Regulation

  1. Activators have separate DNA-binding and activating functions
  1. Eukaryotic regulators use a range of DNA-binding domains, but DNA recognition involves the same principles as found in bacteria
  1. Activating Regions are not well-defined structures

Homeodomain proteins, Zinc-containing DNA-binding domains, Leucine zipper motif, helix-loop-helix proteins, HMG proteins

  1. Activators recruit the transcriptional machinery to the gene
  1. Activators also recruit nucleosome modifiers that help the transcriptional machinery bind at the promoter or initiate transcription
  1. Activators recruit additional factors needed for efficient initiation or elongation at some promoters
  1. Action at a distance: Loops and insulators
  1. Appropriate regulation of some groups of genes requires locus control regions
  1. Activators work synergistically to integrate signals
  1. Signal integration: the HO gene is controlled by two regulators - one recruits the nucleosome modifiers, and the other recruits mediator
  1. Signal integration: cooperative binding of activators at the human β-Interferon gene
  1. Combinatorial control lies at the heart of the complexity and diversity of eukaryotes
  1. Combinatorial control of the mating-type genes from S. cerevisiae
  1. Signals are often communicated to transcriptional regulators through signal transduction pathways
  1. Signals control the activities of eukaryotic transcriptional regulators in a variety of ways
  1. Silencing in yeast is mediated by deacetylation and methylation of histones
  1. In drosophila, HP1 recognizes methylated histones and condenses chromatin
  1. Repression by polycomb also uses histone methylation
  1. DNA methylation is associated with silenced genes in mammalian cells
  1. Some states of gene expression are inherited through cell division even when the initiating signal is no longer present