Chromosome structure and chemical modifications can affect gene expression DNA packing Student Misconceptions and Concerns  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. 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 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.  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.  Just as a folded map is difficult to read, DNA packaging tends to prevent gene reading or expression.  The website http://learn.genetics.utah.edu/content/epigenetics/ has a large section devoted to teaching about epigenetics. This is an excellent resource for students and instructors.  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.

Chromosome structure and chemical modifications can affect gene expression Methylation- Chemical modification of DNA bases or histone proteins can result in epigenetic inheritance

Cell division and random X chromosome inactivation Chromosome structure and chemical modifications can affect gene expression X inactivation Early Embryo Adult Two cell populations Cell division and random X chromosome inactivation X chromosomes Active X Inactive X Orange fur Figure 11.2b-0 A tortoiseshell pattern on a female cat, a result of X chromosome inactivation Inactive X Active X Allele for orange fur Allele for black fur Black fur

The Control of Gene Expression Each cell in the human contains all the genetic material for the growth and development of a human. Some of these genes will be need to be expressed all the time. These are the genes that are involved in of vital biochemical processes such as respiration. Other genes are not expressed all the time. They are switched on an off at need.

Operons An operon is a group of genes that are transcribed at the same time. They usually control an important biochemical process. They are only found in prokaryotes.

Different ways to Regulate Metabolism Feedback inhibition block transcription

Tryptophan operon Repressor is inactive alone

Lactose operon Repressor is active alone

lac operon z y a O Blocked Lactose absent Regulator gene lac operon Operator site z y a DNA I O Repressor protein RNA polymerase Blocked

Activator protein steadies the RNA polymerase Promotor site z y a DNA I O Lactose present Promotor site z y a DNA I O Transcription Activator protein steadies the RNA polymerase

Complex assemblies of proteins control EUKARYOTIC transcription In eukaryotes, activator proteins seem to be more important than repressors. Thus, in multicellular eukaryotes, 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. Eukaryotic RNA polymerase requires the assistance of proteins called transcription factors. RNA polymerase then attaches to the promoter, and transcription begins. Student Misconceptions and Concerns  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. 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 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 the lab, you might relate these degrees of adjustment to the coarse and fine control knobs of a microscope.

Animation: Initiation of Transcription

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

Eukaryotic RNA may be spliced in more than one way Alternative RNA splicing produces different mRNAs from the same transcript and results in the production of more than one polypeptide from the same gene. In humans, more than 90% of protein-coding genes appear to undergo alternate splicing. Student Misconceptions and Concerns  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. 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.

Animation: RNA Processing

Small RNAs play multiple roles in controlling gene expression Only about 1.5% of the human genome codes for proteins. (This is also true of many other multicellular eukaryotes.) Another small fraction of DNA consists of genes for ribosomal RNA and transfer RNA. A flood of recent data suggests that a significant amount of the remaining genome is transcribed into functioning but non-protein-coding RNAs, including a variety of small RNAs. Student Misconceptions and Concerns  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. 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  Recent references in older books and outdated websites may characterize DNA that does not code for rRNA, tRNA, or mRNA as “junk DNA.” The relatively recent discovery of miRNA and its significant roles in gene regulation reveals the danger of concluding that the absence of evidence is evidence of absence!  Describing the discovery of miRNAs and their potential in research and medicine help to illustrate the promise of gene regulation research. Students early in their science careers may appreciate knowing about scientific fields with great potential as they consider the direction of their developing careers.

Small RNAs play multiple roles in controlling gene expression microRNAs (miRNAs) can bind to complementary sequences on mRNA molecules either degrading the target mRNA or blocking its translation. RNA interference (RNAi) is the use of miRNA to artificially control gene expression by injecting miRNAs into a cell to turn off a specific gene sequence. Student Misconceptions and Concerns  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. 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  Recent references in older books and outdated websites may characterize DNA that does not code for rRNA, tRNA, or mRNA as “junk DNA.” .” The relatively recent discovery of miRNA and its significant roles in gene regulation reveals the danger of concluding that the absence of evidence is evidence of absence!  Describing the discovery of miRNAs and their potential in research and medicine help to illustrate the promise of gene regulation research. Students early in their science careers may appreciate knowing about scientific fields with great potential as they consider the direction of their developing careers.

The flow of genetic information from a chromosome to a protein is controlled at several points, just as the flow of water through pipes is controlled by valves. Chromosome DNA unpacking Gene NUCLEUS DNA Transcription Exon Splicing Intron CYTOPLASM RNA transcript Addition of a cap and tail mRNA in nucleus Tail Flow through nuclear envelope Cap mRNA in cytoplasm Breakdown of mRNA Broken-down mRNA Figure 11.7-8 Multiple mechanisms regulate gene expression in eukaryotes (step 8) Translation Polypeptide Cleavage, modification, activation Active protein Breakdown of protein Amino acids