1 and 3 November, 2006

Chapter 17

Regulation in Eukaryotes

Overview• Transcriptional initiation is the most common point to regulate gene expression.• Eukaryotes must also integrate more signals, and must modify nucleosome

positioning in order to activate transcription.• Eukaryotic transcriptional activators are often modular, with DNA binding and

activation domains.• Eukaryotic transcriptional activators may bind as heterodimers.• Classes of eukaryotic transcriptional activators include homeodomain, zinc finger,

leucine zipper, and helix-loop-helix.• Activators recruit the transcriptional machinery to the gene, interacting with

mediator or TFII general factors.• Activators may also promote chromatin modification.• Insulators block activation by enhancers.• Locus control regions open up chromatin to regulation by activators.• Activators act synergistically.• Eukaryotic transcription may be repressed by blocking or binding activators,

interacting with mediator, or by modifying chromatin.• Signal transduction pathways communicate with transcriptional regulators.• DNA and histone modification can collaborate to effect regulation.• Regulation may also occur at the levels of splicing, translation, and RNA stability.

Complex Eukaryotic Regulatory Regions

Modular Transcriptional Activators

The Two-hybrid System Again!

Homeodomain

Zinc Finger

Leucine Zipper

Helix-Loop-Helix

Potential Activator Contacts

Activator Bypass by LexA-Mediator Fusion

ChIP can identify

binding sites.

Binding and Recruitment Assay

Gal4 recruits TFIIB

Activators may promote histone acetylation and / or chromatin remodeling.

Insulators block the effects of activators at enhancers.

Locus control regions make clusters of genes available for activation.

Possible Modes of

Cooperative Binding of Activators

Synergistic Action of SWI5 and SBF in HO Expression

Signal integration at the INF- gene

Combinatorial Control

Control of Cell-type Specific Genes in Yeast

Possible Modes of Action for Eukaryotic Repressors.

Signal transduction

pathways regulate

transcription factors.

Gal80 Regulates Gal4

Silencing through Histone Deacetylation

Silencing sometimes involves methylation and histone deacetylation.

Imprinting

Methylation patterns are heritable.

Transcriptional Regulation of Sxl

Regulated Alternative

Splicing

Translational Control of

GCN4

RNAi

Cooperative and Non-Cooperative Binding

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