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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