12.1: Introduction

Cells regulate their metabolism in several ways. We have already seen that allosterically regulated enzymes monitor the cellular levels of metabolites. Recall that the glycolytic intermediates rise and fall in cells based on cellular energy needs, binding to or dissociating from allosteric sites. In response to interactions with allosteric effectors, allosteric enzymes cause an increase or decrease in catalytic activity.

Cells can also control absolute levels of enzymes and other proteins by turning genes on and off, typically by controlling transcription. Transcription regulation usually starts with extracellular environmental signaling. The signals are chemicals in the air, in the water, or (in the case of multicellular organisms) in the blood, lymph, or other extracellular fluids. Bacterial and protist genes often respond to environmental toxins or fluctuating nutrient levels. Familiar signal molecules in higher organisms include hormones, which are released at the appropriate time in a sequential developmental program of gene expression or in response to nutrient levels in body fluids.

Some signal molecules enter cells and bind to specific intracellular receptors to convey their instructions. Others bind to cell surface receptors, which transduce their “information” into intracellular molecular signals. When signals indicate the need for gene regulation, responding cells ultimately produce transcription factors. These in turn recognize and bind to specific regulatory DNA sequences associated with the genes that they control.

DNA sequences that bind transcription factors are relatively short. They can lie proximal (close) to the transcription start site of a gene, and/or (in the case of eukaryotes) distal to (far from) it. We will see that some of these regulatory DNA sequences are enhancers, turning on or increasing gene transcription. Others are silencers, down-regulating or suppressing transcription of a gene. Finally, DNA regulatory sequences are hidden behind a thicket of chromatin proteins in eukaryotes. When patterns of gene expression in cells change during development, chromatin is reorganized; cells differentiate; and new tissues and organs form. To this end, new patterns of gene expression and chromatin configuration in a cell need to be remembered by its descendants.

In this chapter, we look at the path from cell recognition of a signal molecule to the interaction of regulatory proteins with DNA in prokaryotic and with DNA and chromatin in eukaryotic cells. We also consider how eukaryotic cells remember and pass on to their progeny instructions that alter chromatin configuration and patterns of gene expression—topics in the field of epigenetics.

Learning Objectives

When you have mastered the information in this chapter, you should be able to:

1. Compare and contrast transcription factors and so-called cis-acting elements.
2. Discuss the role of DNA bending in the regulation of gene expression.
3. Explain the benefits of organizing bacterial genes into operons, and why some bacterial genes are not part of operons
4. Compare and contrast regulation of the lac and trp operons in E. coli.
5. Define and describe regulatory genes and structural genes in E. coli.
6. Discuss why a fourth gene was suspected in lac operon regulation.
7. Distinguish between gene repression and de-repression and between positive and negative gene regulation, using examples. For example, explain how it is possible to have repression by positive regulation.
8. Draw and label all functional regions of prokaryotic and eukaryotic genes.
9. Compare and contrast different mechanisms of gene regulation in eukaryotic cells.
10. Describe the transcription initiation complex of a regulated gene in eukaryotes.
11. Define and articulate differences between gene expression and transcription regulation.
12. Define a gene
13. Distinguish between the roles of enhancers and other cis-acting elements in transcription regulation.
14. Compare and contrast the genome and the epigenome.