AP Biology 6.5-6.6: Regulation of Gene Expression

Silencer

A DNA sequence that decreases transcription when bound by appropriate regulatory proteins, often called repressors or silencer-binding transcription factors.

Gene expression

The process by which information in a gene is used to produce a functional RNA or protein. Cells regulate gene expression to control when, where, and how much gene product is made.

Why do cells regulate gene expression instead of expressing all genes continuously?

Regulation conserves energy and cellular space by producing proteins only when needed. It also allows cells to specialize, respond to environmental conditions, and avoid harmful or unnecessary protein activity.

How can different cell types arise even though they generally contain the same genome?

Different cell types selectively express different subsets of genes. Their distinct gene-expression profiles produce different proteins and therefore different structures and functions.

How can gene regulation help a cell respond to environmental change?

Regulatory proteins and signaling pathways detect conditions such as nutrient availability or stress and alter transcription, RNA fate, translation, or protein activity. The cell can then produce proteins suited to the current environment.

What is the primary level of gene-expression control in prokaryotes, and why?

Control occurs primarily at transcription. Because prokaryotes lack a nucleus, transcription and translation occur nearly simultaneously, leaving fewer opportunities to regulate gene expression between these processes.

How are transcription and translation spatially organized in eukaryotic cells?

Transcription occurs in the nucleus, while translation occurs in the cytoplasm. The nuclear membrane separates these processes and creates additional opportunities for regulation.

Why does compartmentalization increase regulatory complexity in eukaryotes?

Separating DNA transcription in the nucleus from translation in the cytoplasm creates additional control points, including RNA processing, export, localization, and degradation. Eukaryotes can therefore regulate gene expression at more stages than most prokaryotes.

Compare gene-expression regulation in prokaryotes and eukaryotes.

Prokaryotes regulate expression mainly by controlling transcription in the cytoplasm. Eukaryotes can regulate chromatin accessibility, transcription, RNA processing and export, translation, and protein modification or degradation.

At what stages can eukaryotic gene expression be regulated after transcription begins?

Regulation can occur during RNA processing, nuclear export, mRNA stability, translation, protein modification, and protein degradation. These controls determine how much functional protein is ultimately present.

Epigenetic regulation

Regulation of gene activity through changes in chromatin or chemical modifications associated with DNA and histones without changing the DNA nucleotide sequence. Some epigenetic states can persist through cell division.

Nucleosome

A structural unit of chromatin consisting of DNA wrapped around a core of histone proteins. Nucleosome positioning and histone modifications influence whether nearby genes are accessible for transcription.

What is the relationship between chromatin structure and transcription?

Loosely packed chromatin is generally more accessible to transcription factors and RNA polymerase, increasing transcriptional potential. Densely packed chromatin restricts access and usually decreases gene expression.

How does histone acetylation generally affect gene expression?

Histone acetylation typically reduces the positive interaction between histones and negatively charged DNA, loosening chromatin and increasing DNA accessibility. It is therefore often associated with increased transcription.

DNA methylation

The addition of methyl groups to DNA, commonly to cytosine residues in CpG sites in mammals. Methylation in a promoter region is often associated with reduced transcription.

CpG site

A DNA sequence in which cytosine is followed by guanine on the same strand. Clusters of CpG sites in promoter regions can be targets for methylation-based regulation.

How does promoter methylation usually affect transcription?

Methylation of CpG sites in a promoter commonly represses transcription by interfering with transcription-factor binding and/or recruiting proteins that compact chromatin. The effect depends on genomic context, but promoter methylation is generally associated with gene silencing.

How can histone deacetylation and DNA methylation cooperate to silence a gene?

Histone deacetylation promotes tighter chromatin packing, while methylation of regulatory DNA can reduce transcription-factor binding or recruit repressors. Together, they commonly decrease access to the promoter and repress transcription.

Transcriptional regulation

Control of whether transcription begins and how frequently RNA polymerase produces RNA from a gene. It is a major control point in both prokaryotic and eukaryotic cells.

Promoter

A DNA region near the beginning of a gene where RNA polymerase and associated transcription factors assemble to initiate transcription.

Repressor

A regulatory protein that decreases gene expression, often by binding DNA and preventing RNA polymerase from initiating or continuing transcription.

Activator

A regulatory protein that increases transcription by promoting RNA polymerase recruitment or changing DNA structure to facilitate formation of the transcription-initiation complex.

Operator

A regulatory DNA sequence, common in prokaryotic operons, that can bind a repressor near or overlapping the promoter. Repressor binding can obstruct RNA polymerase and reduce transcription.

Enhancer

A regulatory DNA sequence bound by activator proteins that increases transcription from a target promoter. In eukaryotes, DNA looping can bring an enhancer-bound activator into contact with the promoter.

General transcription factors versus specific transcription regulators

General transcription factors help position and recruit RNA polymerase at a promoter for transcription initiation. Specific activators and repressors alter expression of particular genes or groups of genes in response to cellular signals.

How does a repressor bound to an operator affect RNA synthesis?

The repressor can physically block RNA polymerase from binding the promoter or moving along the DNA template. As a result, transcription of the associated gene or operon decreases.

lac operon

A bacterial gene-regulatory system for lactose metabolism in which regulatory proteins control transcription of multiple genes involved in using lactose. Lactose availability and glucose availability influence whether the operon is strongly expressed.

What is the advantage of organizing related bacterial genes in an operon?

Genes for a common pathway can be transcribed together and regulated by the same promoter and operator. This allows coordinated, energy-efficient responses to environmental conditions.

What happens to lactose-metabolism genes when lactose is absent in the lac operon?

A repressor binds the operator and obstructs transcription of the operon. This prevents the cell from producing large amounts of lactose-metabolism enzymes when lactose is unavailable.

How does lactose activate transcription of the lac operon?

Lactose, through its isomer allolactose, binds to and changes the shape of the lac repressor. The repressor then releases the operator, allowing transcription of the lactose-metabolism genes.

How does glucose availability affect lac operon expression?

When glucose is scarce, cAMP levels rise and cAMP binds the catabolite activator protein (CAP). The CAP–cAMP complex binds near the lac promoter and helps recruit RNA polymerase, producing high transcription when lactose is also present.

Under what conditions is the lac operon expressed at its highest level?

The lac operon is expressed most strongly when lactose is present and glucose is scarce. Lactose removes repressor activity, while low glucose allows the cAMP–CAP activator complex to stimulate transcription.

trp operon

A repressible bacterial operon containing genes for tryptophan synthesis. It is generally transcribed when tryptophan is scarce and repressed when tryptophan is abundant.

How does tryptophan regulate the trp operon?

When tryptophan is abundant, it binds to the trp repressor and acts as a corepressor. The activated repressor binds the operator and prevents transcription of genes needed to synthesize more tryptophan.

Compare the lac and trp operons.

The lac operon is inducible: it is activated when lactose is available, especially when glucose is scarce. The trp operon is repressible: it is shut down when its end product, tryptophan, is abundant.

Post-transcriptional regulation

Regulation of gene expression after an RNA transcript is produced but before or during its translation. It includes RNA capping, splicing, polyadenylation, nuclear export, sequestration, degradation, and control by regulatory RNAs.

How can RNA processing alter the amount of functional protein produced?

Capping, splicing, poly(A)-tail addition, and export affect whether an mRNA is stable, transported to the cytoplasm, and recognized by ribosomes. Alternative processing can also allow different RNAs or proteins to be produced from one gene.

What is the role of an mRNA 3′ untranslated region (3′-UTR) in gene regulation?

The 3′-UTR contains regulatory sequences that can bind microRNAs and regulatory proteins. These interactions can alter mRNA stability, degradation, localization, or translation efficiency without changing the protein-coding sequence.

MicroRNA (miRNA)

A short noncoding RNA that binds complementary sequences, often in an mRNA 3′-UTR. Binding can inhibit translation or promote degradation of the target mRNA, reducing production of its protein.

How can a single microRNA influence many genes?

A microRNA can recognize related sequence patterns in the 3′-UTRs of many different mRNAs. Therefore, one miRNA may modestly repress the translation or stability of numerous transcripts.

How can translation initiation be regulated?

Cells can alter recruitment of the small ribosomal subunit by changing mRNA secondary structure or by using regulatory proteins or antisense RNA. Reduced ribosome recruitment generally decreases protein synthesis from that mRNA.

Why can mRNA secondary structure affect translation?

Folding near the translation-initiation region can hide sequences needed for ribosome binding. Conditions such as temperature or ligand binding can change RNA folding and thereby alter translation efficiency.

Post-translational regulation

Regulation that occurs after a protein is synthesized, including chemical modification, changes in localization or activity, and degradation. It can rapidly alter the amount or function of an existing protein.

How does protein degradation influence gene-expression output?

The functional protein level depends on both its synthesis rate and its degradation rate. Faster degradation lowers protein abundance even if translation remains unchanged, whereas greater stability can increase protein abundance.

What determines the final amount of an active protein in a cell?

It depends on the rates of transcription, RNA processing and degradation, translation, post-translational activation or inactivation, and protein degradation. Regulation at any of these stages can change the final functional protein level.

Gene regulatory network

A network in which regulatory genes and proteins control the expression of other genes, often through cascading interactions. Such networks coordinate complex responses, developmental programs, and cell-type-specific expression.

How can gene regulation contribute to development and cellular differentiation?

Signals activate or repress different sets of genes in cells during development. These changing expression patterns produce distinct proteins, structures, and functions even among cells with the same genome.

How can abnormal gene regulation contribute to cancer?

Aberrant DNA methylation, altered chromatin regulation, transcription-factor activity, or microRNA expression can inappropriately silence tumor-suppressor genes or activate growth-promoting genes. Such regulatory changes can promote uncontrolled cell proliferation even without a mutation in every affected gene.