Gene Regulation in Eukaryotes

Introduction

A.     Requirements for regulation

    1. As a response to changing environments (as with prokaryotes)
    2. As a mechanism that underlies development

B.     General aspects of eukaryotic regulation

Strategies based on the state of DNA

A.     Gene amplification

B.     Cytosine methylation

    1. CG islands and methylation-induced silencing of genes
    2. housekeeping vs tissue-specific genes
    3. de novo vs maintenance methylation as a mechanism for achieving tissue-specific expression

C.     Chromatin decondensation

    1. closed vs. open chromatin
    2. DNaseI hypersensitivity

Regulation of Transcription (click here for an exceptionally good recent review)

A.     Response elements

    1. Enhancers
    2. Silencers
    3. Loops

B.     Transcription factors

    1. Role and importance of oncogenes in discovery
    2. Families of transcription factors based on DNA binding domains

a.       helix-turn-helix

b.      zinc finger

c.       leucine zipper

d.      bHLH

    1. Importance of dimerization
    2. Regulons and cross-talk in global regulatory networks

C.     Mechanisms

    1. Concepts of positive and negative regulation still apply, but need some elaboration and extensions

 .        hormones as effectors (e.g., glucocorticoid hormone/receptor) as formal equivalent of positive regulation in bacteria

a.       protein-protein interactions (c-jun + c-fos = AP1)

b.      covalent modification, particularly phosphorylation (see CREB example in text)

    1. Two-component regulatory systems in prokaryotes and eukaryotes