Lecture12 - Based on Chapter 18 - Regulation of Gene Expression in Eukaryotes I Copyright © 2010 Pearson Education Inc.

1 -Levels of Control of Gene Expression in Eukaryotes Previously we discussed aspects of transcription that involved the production of a primary transcript and the processing of this into aspects of how this is processed into an mRNA in Eukaryotes. This lecture focuses on these topics and on how signals are perceived that modulate the expression of eukaryotic genes. The next lecture will examine the details of controlling gene expression post- transcriptionally.

2 - Control of Transcription Initiation by Regulatory Proteins 1.In eukaryotes, control of gene expression is at the level of transcription initiation 2.Controlled by promoter (immediately upstream) and enhancers (distal from the gene). a.Expression from the promoter alone is at basal level. b.For maximal transcription, activator proteins bind to: i.Promoter-proximal elements ii.Enhancer elements 3. Binding of activators: a.Recruits proteins that make the chromatin accessible to the transcription machinery. b.Increases binding of the transcription machinery to the promoter. 4. Repressors are also used to decrease or prevent transcription.

3 – Regulation of Transcription Initiation by Activators

4 - Regulation of Transcription Initiation by Activators II

5 – Inhibiting transcription Initiation by Repressors 1. Repressors inhibit activation of transcription by activators. a. Two domains occur in repressors, a DNA-binding region and a repressing domain. b. Repressors work in a variety of ways. Examples: i. Repressor binds near activator’s binding site, and repressor domain interacts with activation domain of the activator, preventing activation. ii. Repressor binding site overlaps activator binding site, preventing activator binding. iii. Chromatin remodeling can also block transcription if repressor binds its site and recruits HDAC (histone deacetylase) to cause chromatin compaction.

10 - Combinatorial Gene Regulation: The Control of Transcription by Combinations of Activators and Repressors

6 - Case Study: Positive and Negative Regulation of Transcription of the Yeast Galactose Utilization Genes

7 - Case Study: Regulation of Transcription in Animals by Steroid Hormones I

8 - Case Study: Regulation of Transcription in Animals by Steroid Hormones II

9 - Case Study: Regulation of Transcription in Animals by Steroid Hormones III

7 – Case Study: Peptide Hormone Receptors

Case Study: Insulin Signaling Pathway

1 -Levels of Control of Gene Expression in Eukaryotes

12 – Gene Silencing and Genomic Imprinting

13 – Gene Silencing by DNA Methylation

14 – Genomic Imprinting

1 -Levels of Control of Gene Expression in Eukaryotes