Regulation and Control of Gene Expression

15.1 Gene Expression in Eukaryotic Cells  Gene controls govern the kinds and amounts of substances in a cell at any given interval  Various control processes regulate all steps between gene and gene product

Which Genes Get Tapped?  Differentiation The process by which cells become specialized In multicelled organisms, most cells differentiate when they start expressing a unique subset of their genes Which genes are expressed depends on the type of organism, its stage of development, and environmental conditions

Control of Transcription  Transcription factors Regulatory proteins that affect the rate of transcription by binding to special nucleotide sequences in DNA Activators speed up transcription when bound to a promoter; or may bind to distant enhancers Repressors slow or stop transcription

Control of Transcription  Chemical modifications and chromosome duplications affect RNA polymerase’s access to genes Interactions between DNA and histone proteins (methylation) prevent transcription Polytene chromosomes (many copies) increase transcription rates in some organisms

Controls of mRNA Transcripts  mRNA processing DNA splicing controls products of translation  mRNA transport controls delivery of transcripts Passage through nuclear pores Delivery within cytoplasm (mRNA localization)

Translational Controls  Controls over molecules involved in translation  Controls over mRNA stability Depends on base sequence, length of poly-A tail, and which proteins are attached to it  RNA interference Expression of a microRNA complementary to a gene inhibits expression of the gene

Post-Translational Modification  Post-translational modification can inhibit, activate, or stabilize many molecules, including enzymes that participate in transcription and translocation

Points of Control over Eukaryotic Gene Expression

DNA NUCLEUS A Transcription Binding of transcription factors to special sequences in DNA slows or speeds transcription. Chemical modifications and chromosome duplications affect RNA polymerase’s physical access to genes. new RNA transcript B mRNA Processing New mRNA cannot leave the nucleus before being modified, so controls over mRNA processing affect the timing of transcription. Controls over alternative splicing influence the final form of the protein. mRNA Fig. 15-2, p. 230 Stepped Art mRNA CYTOPLASM C mRNA Transport RNA cannot pass through a nuclear pore unless bound to certain proteins. Transport protein binding affects where the transcript will be delivered in the cell. polypeptide chain D Translation An mRNA’s stability influences how long it is translated. Proteins that attach to ribosomes or initiation factors can inhibit translation. Double- stranded RNA triggers degradation of complementary mRNA. active protein E Protein Processing A new protein molecule may become activated or disabled by enzyme- mediated modifications, such as phosphorylation or cleavage. Controls over these enzymes influence many other cell activities.

15.1 Key Concepts: Overview of Controls Over Gene Expression  A variety of molecules and processes alter gene expression in response to changing conditions both inside and outside the cell  Selective gene expression also results in cell differentiation, by which different cell lineages become specialized

15.2 A Few Outcomes of Eukaryotic Gene Controls  Selective gene expression can give rise to visible traits

X Chromosome Inactivation  X chromosome inactivation In cells of female mammals, either the maternal or paternal X chromosome is randomly condensed (Barr body) and is inactive Occurs in an early embryonic stage, so that all descendents of that particular cell have the same inactive X chromosome, resulting in “mosaic” gene expression

X Chromosome Inactivation

Calico: Mosaic Gene Expression in a Female Mammal

Prokaryotic Gene Control  In prokaryotes, genes that are used together often occur together on chromosomes  Operon A promoter and one or more operators that collectively control transcription of multiple genes  Operators DNA regions that are binding sites for a repressor

The Lactose Operon  E. coli digest lactose in guts of mammals using a set of three enzymes controlled by two operators and a single promoter (the lac operon) When lactose is not present, repressors bind to the operators and inactivate the promoter; transcription does not proceed When lactose is present, allolactose binds to the repressors; repressors don’t bind to operators to inactivate the promoter; transcription proceeds

The Lactose Operon Repressor

Lactose Intolerance  Human infants and other mammals produce the enzyme lactase, which digests the lactose in milk – adults tend to lose the ability to produce lactase, and become lactose intolerant