1. How Genes Are Controlled
Chapter 11
How Genes Are Controlled

2. Regulation of Eukaryotic Gene Expression
Prokaryotes and eukaryotes employ regulatory proteins that
bind to specific segments of DNA and
either promote or block the binding of RNA polymerase, turning the transcription of genes on and off.
In eukaryotes, activator proteins seem to be more important than repressors. Thus, the default state for most genes seems to be off.
A typical plant or animal cell needs to turn on and transcribe only a small percentage of its genes.
Student Misconceptions and Concerns
1. The broad concept of selective reading of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation.
2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.7 can be a helpful reference to organize the potential sites of regulation.
Teaching Tips
The authors note that the selective unpackaging of chromosomes is the “coarse adjustment” of eukaryotic gene expression. The initiation of RNA synthesis is the fine-tuning of the regulation. If you have recently asked your students to use microscopes in lab, you might relate these degrees of adjustment to the coarse and fine control knobs of a microscope.
© 2012 Pearson Education, Inc. 2

3. Regulation of Eukaryotic Gene Expression
Eukaryotes also need to regulate gene expression during embryonic development
Differentiation = cell specialization, in structure and function
is controlled by turning specific sets of genes on or off.
Almost all of the cells in an organism contain an identical genome.
The differences between cell types are due to selective gene expression.
Student Misconceptions and Concerns
1. The broad concept of selective reading of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation.
2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.7 can be a helpful reference to organize the potential sites of regulation.
Teaching Tips
1. The control of gene expression is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type.
2. Just as boxes of things that you rarely use are packed into a closet, attic, or basement, chromatin that is not expressed is highly compacted, and stored deeply packed away.
3. Just as a folded map is difficult to read, DNA packaging tends to prevent gene reading or expression.
4. Students might wonder why a patch of color is all the same on a cat’s skin if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation.
© 2012 Pearson Education, Inc. 3

4. Root cells cultured in growth medium Cell division in culture
Figure 11.12
Root of carrot plant
Single cell
Figure Growth of a carrot plant from a differentiated root cell
Root cells cultured in growth medium
Cell division in culture
Plantlet
Adult plant 4

5. Figure 11.7 The gene expression “pipeline” in a eukaryotic cell
Chromosome
Chromosome
DNA unpacking Other changes to the DNA
Gene
DNA
Transcription
Gene
Exon
RNA transcript
Intron
Addition of a cap and tail
Splicing
Tail
Cap
mRNA in nucleus
Flow through nuclear envelope
NUCLEUS
CYTOPLASM
mRNA in cytoplasm
Breakdown of mRNA
Broken- down mRNA
Translation
Figure 11.7 The gene expression “pipeline” in a eukaryotic cell
Polypeptide
Polypeptide
Cleavage, modification, activation
Active protein
Active protein
Breakdown of protein
Amino acids 5

6. DNA Packaging and Modification
Eukaryotic chromosomes undergo multiple levels of folding and coiling
Nucleosomes are formed when DNA is wrapped around histone proteins.
Each nucleosome bead includes DNA plus eight histones.
DNA double helix (2-nm diameter)
“Beads on a string”
Linker
Histones
Supercoil (300-nm diameter)
Nucleosome (10-nm diameter)
Tight helical fiber (30-nm diameter)
Metaphase chromosome
700 nm
Student Misconceptions and Concerns
1. The broad concept of selective reading of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation.
2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.7 can be a helpful reference to organize the potential sites of regulation.
Teaching Tips
1. The control of gene expression is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type.
2. Just as boxes of things that you rarely use are packed into a closet, attic, or basement, chromatin that is not expressed is highly compacted, and stored deeply packed away.
3. Just as a folded map is difficult to read, DNA packaging tends to prevent gene reading or expression.
4. Students might wonder why a patch of color is all the same on a cat’s skin if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation. 6

7. DNA Packaging and chemical modifications can affect gene expression
DNA packing can prevent gene expression by preventing RNA polymerase from contacting the DNA.
More tightly compacted DNA - less likely DNA will be transcribed
Euchromatin - transcriptional active regions of DNA
Heterochromation - transcriptional silent (highly compacted)
Student Misconceptions and Concerns
1. The broad concept of selective reading of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation.
2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.7 can be a helpful reference to organize the potential sites of regulation.
Teaching Tips
1. The control of gene expression is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type.
2. Just as boxes of things that you rarely use are packed into a closet, attic, or basement, chromatin that is not expressed is highly compacted, and stored deeply packed away.
3. Just as a folded map is difficult to read, DNA packaging tends to prevent gene reading or expression.
4. Students might wonder why a patch of color is all the same on a cat’s skin if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation.
Animation: DNA Packing
© 2012 Pearson Education, Inc. 7

8. DNA Packaging and chemical modifications can affect gene expression
Methylation of DNA
Certain enzymes can add a methyl group to DNA bases, without changing the sequence of the bases.
Methylation generally inhibits gene expression
Example: X-Chromosome inactivation
Student Misconceptions and Concerns
1. The broad concept of selective reading of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation.
2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.7 can be a helpful reference to organize the potential sites of regulation.
Teaching Tips
1. The control of gene expression is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type.
2. Just as boxes of things that you rarely use are packed into a closet, attic, or basement, chromatin that is not expressed is highly compacted, and stored deeply packed away.
3. Just as a folded map is difficult to read, DNA packaging tends to prevent gene reading or expression.
4. Students might wonder why a patch of color is all the same on a cat’s skin if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation.
© 2012 Pearson Education, Inc. 8

9. DNA packaging and chemical modifications can affect gene expression
X-chromosome inactivation
In female mammals, one of the two X chromosomes is highly compacted and transcriptionally inactive.
An inactivated X chromosome is called a Barr body.
Student Misconceptions and Concerns
1. The broad concept of selective reading of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation.
2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.7 can be a helpful reference to organize the potential sites of regulation.
Teaching Tips
1. The control of gene expression is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type.
2. Just as boxes of things that you rarely use are packed into a closet, attic, or basement, chromatin that is not expressed is highly compacted, and stored deeply packed away.
3. Just as a folded map is difficult to read, DNA packaging tends to prevent gene reading or expression.
4. Students might wonder why a patch of color is all the same on a cat’s skin if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation.
© 2012 Pearson Education, Inc. 9

10. Cell division and random X chromosome inactivation
Figure 11.2B
Early Embryo
Adult
Two cell populations
Cell division and random X chromosome inactivation
X chromo- somes
Active X
Orange fur
Inactive X
Figure 11.2B A tortoiseshell pattern on a female cat, a result of X chromosome inactivation
Allele for orange fur
Inactive X
Allele for black fur
Active X
Black fur 10

11. Figure 11.7 The gene expression “pipeline” in a eukaryotic cell
Chromosome
Chromosome
DNA unpacking Other changes to the DNA
Gene
DNA
Transcription
Gene
Exon
RNA transcript
Intron
Addition of a cap and tail
Splicing
Tail
Cap
mRNA in nucleus
Flow through nuclear envelope
NUCLEUS
CYTOPLASM
mRNA in cytoplasm
Breakdown of mRNA
Broken- down mRNA
Translation
Figure 11.7 The gene expression “pipeline” in a eukaryotic cell
Polypeptide
Polypeptide
Cleavage, modification, activation
Active protein
Active protein
Breakdown of protein
Amino acids 11

12. Regulation of Transcription
Eukaryotic RNA polymerase requires the assistance of proteins called transcription factors.
Transcription factors recruit RNA polymerase to gene’s promoter
Activator proteins, which bind to DNA sequences called enhancers and help increase rate of gene transcription.
Silencers are repressor proteins that
may bind to DNA sequences and
inhibit transcription.
Student Misconceptions and Concerns
1. The broad concept of selective reading of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation.
2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.7 can be a helpful reference to organize the potential sites of regulation.
Teaching Tips
The authors note that the selective unpackaging of chromosomes is the “coarse adjustment” of eukaryotic gene expression. The initiation of RNA synthesis is the fine-tuning of the regulation. If you have recently asked your students to use microscopes in lab, you might relate these degrees of adjustment to the coarse and fine control knobs of a microscope.
Animation: Initiation of Transcription
© 2012 Pearson Education, Inc. 12

13. Transcription factors
Figure 11.3
Enhancers
Promoter
Gene
DNA
Activator proteins
Transcription factors
Other proteins
RNA polymerase
Figure 11.3 A model for the turning on of a eukaryotic gene
Bending of DNA
Transcription 13

14. Figure 11.7 The gene expression “pipeline” in a eukaryotic cell
Chromosome
Chromosome
DNA unpacking Other changes to the DNA
Gene
DNA
Transcription
Gene
Exon
RNA transcript
Intron
Addition of a cap and tail
Splicing
Tail
Cap
mRNA in nucleus
Flow through nuclear envelope
NUCLEUS
CYTOPLASM
mRNA in cytoplasm
Breakdown of mRNA
Broken- down mRNA
Translation
Figure 11.7 The gene expression “pipeline” in a eukaryotic cell
Polypeptide
Polypeptide
Cleavage, modification, activation
Active protein
Active protein
Breakdown of protein
Amino acids 14

15. Regulation of mRNA Processing
Alternative RNA splicing
produces different mRNAs from the same transcript,
results in the production of more than one polypeptide from the same gene
Animation: RNA Processing
DNA
RNA transcript
mRNA
Exons
Introns
Cap
Tail
RNA splicing or 1 2 4 5 3
Student Misconceptions and Concerns
1. The broad concept of selective reading of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation.
2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.7 can be a helpful reference to organize the potential sites of regulation.
Teaching Tips
Alternative RNA splicing is like remixing music to produce a new song or re-editing a movie for a different effect.
© 2012 Pearson Education, Inc. 15

16. Figure 11.7 The gene expression “pipeline” in a eukaryotic cell
Chromosome
Chromosome
DNA unpacking Other changes to the DNA
Gene
DNA
Transcription
Gene
Exon
RNA transcript
Intron
Addition of a cap and tail
Splicing
Tail
Cap
mRNA in nucleus
Flow through nuclear envelope
NUCLEUS
CYTOPLASM
mRNA in cytoplasm
Breakdown of mRNA
Broken- down mRNA
Translation
Figure 11.7 The gene expression “pipeline” in a eukaryotic cell
Polypeptide
Polypeptide
Cleavage, modification, activation
Active protein
Active protein
Breakdown of protein
Amino acids 16

17. 11.6 Later stages of gene expression are also subject to regulation
After mRNA is fully processed and transported to the cytoplasm, gene expression can still be regulated by
breakdown of mRNA,
initiation of translation,
protein activation, and
protein breakdown.
Animation: Blocking Translation
Animation: mRNA Degradation
Animation: Protein Degradation
Student Misconceptions and Concerns
1. The broad concept of selective reading of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation.
2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.7 can be a helpful reference to organize the potential sites of regulation.
Teaching Tips
The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from a local water supply, perhaps a reservoir, to a faucet. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.7 illustrates the flow of genetic information from a chromosome—a reservoir of genetic information—to an active protein that has been made in the cell’s cytoplasm. The multiple mechanisms that control gene expression are analogous to the control valves in water pipes. In the figure, a possible control knob indicates each gene expression “valve.” The larger size of the transcription control knob highlights its crucial role.
Animation: Protein Processing
© 2012 Pearson Education, Inc. 17

18. Figure 11.7 The gene expression “pipeline” in a eukaryotic cell
Chromosome
Chromosome
DNA unpacking Other changes to the DNA
Gene
DNA
Transcription
Gene
Exon
RNA transcript
Intron
Addition of a cap and tail
Splicing
Tail
Cap
mRNA in nucleus
Flow through nuclear envelope
NUCLEUS
CYTOPLASM
mRNA in cytoplasm
Breakdown of mRNA
Broken- down mRNA
Translation
Figure 11.7 The gene expression “pipeline” in a eukaryotic cell
Polypeptide
Polypeptide
Cleavage, modification, activation
Active protein
Active protein
Breakdown of protein
Amino acids 18

19. Initial polypeptide (inactive) Folded polypeptide (inactive)
Figure 11.6 SH SH
Folding of the polypeptide and the formation of S—S linkages S S S S SH S
Cleavage S SH SH S S SH S S S S
Initial polypeptide (inactive)
Folded polypeptide (inactive)
Active form of insulin
Figure 11.6 Protein activation: the role of polypeptide cleavage 19

20. 11.7 Review: Multiple mechanisms regulate gene expression in eukaryotes
These controls points include:
chromosome changes and DNA unpacking,
control of transcription,
control of RNA processing including the
addition of a cap and tail and
splicing,
flow through the nuclear envelope,
breakdown of mRNA,
Student Misconceptions and Concerns
1. The broad concept of selective reading of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation.
2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.7 can be a helpful reference to organize the potential sites of regulation.
Teaching Tips
The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from a local water supply, perhaps a reservoir, to a faucet. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.7 illustrates the flow of genetic information from a chromosome—a reservoir of genetic information—to an active protein that has been made in the cell’s cytoplasm. The multiple mechanisms that control gene expression are analogous to the control valves in water pipes. In the figure, a possible control knob indicates each gene expression “valve.” The larger size of the transcription control knob highlights its crucial role.
© 2012 Pearson Education, Inc. 20

21. 11.7 Review: Multiple mechanisms regulate gene expression in eukaryotes
control of translation, and
control after translation including
cleavage/modification/activation of proteins and
breakdown of protein.
Student Misconceptions and Concerns
1. The broad concept of selective reading of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation.
2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.7 can be a helpful reference to organize the potential sites of regulation.
Teaching Tips
The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from a local water supply, perhaps a reservoir, to a faucet. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.7 illustrates the flow of genetic information from a chromosome—a reservoir of genetic information—to an active protein that has been made in the cell’s cytoplasm. The multiple mechanisms that control gene expression are analogous to the control valves in water pipes. In the figure, a possible control knob indicates each gene expression “valve.” The larger size of the transcription control knob highlights its crucial role.
© 2012 Pearson Education, Inc. 21