Chp. 12 - Exam 3 Bio 190

Gene Regulation Overview

• Gene regulation is the ability of cells to control the expression of their genes.
• Most genes are regulated to ensure proteins are produced at the correct time and in the correct amount.
• Regulation conserves energy by producing only what is needed.
• Some genes have relatively constant levels of expression; these are constitutive genes. They frequently encode proteins constantly required, like enzymes for carbohydrate metabolism.
• Many proteins regulate gene expression by binding to DNA.

Eukaryotic Gene Regulation

• Enables multicellular organisms to proceed through developmental stages.
• Certain genes are expressed at particular stages.  
• Example: Hemoglobin protein changes throughout development (embryo, fetus, adult). The specific gene expression of different forms of hemoglobin (α- and β-globin sequences) changes with developmental stage.

Gene Regulation Practice Questions

• How do genomes differ among different cell types (e.g. skeletal muscle, neuron, skin cell)?
• How do proteomes differ among different cell types?

Eukaryotic Cell Differentiation

• Cell differentiation is the process by which cells become specialized into particular types.
• Different cells have different specialized functions.

Gene Regulation in Eukaryotes: Points in the Process

• Transcriptional regulation
• RNA modification
• Alternative Splicing
• Translation regulation

Eukaryotic Protein-Encoding Genes

• Include a core promoter and regulatory elements.
• The core promoter contains the TATA box and the transcription start site.
• The core promoter alone results in a low level of basal transcription.

Transcription Factors

• Bind to gene regulatory elements.
• Two types: enhancers and silencers.

RNA Polymerase II

• Transcribes genes that encode proteins.
• Requires five different general transcription factors (GTFs) to initiate transcription.
• GTFs ensure RNA polymerase starts in the right place and facing the correct direction.

Activators and Repressors

• Activators bind to enhancer sequences.
• Repressors bind to silencer sequences.
• They commonly regulate transcription by affecting the function of GTFs.
• TFIID binds the TATA box and is a common target for activators and repressors.
• TFIID plays a critical role in ensuring RNA polymerase is correctly positioned.

Combinatorial Control in Eukaryotes

• Most eukaryotic genes are under combinatorial control.
• This means expression is regulated by the combination of many factors.
• Activators and repressors, and environmental signals influence the expression levels of a gene.

DNA Methylation

• DNA methylation can inhibit gene transcription.
• This adds a methyl group to a DNA base in the gene region.
• The added methyl group can prevent transcription initiation by binding proteins to block the regulatory regions.
• The amount of methylation can be influenced by environmental factors.

Chromatin Structure

• Some genes are buried in tight chromatin.

• Tight conformation blocks RNA polymerase from accessing the DNA, needed to regulate the production of proteins.

• A region in a closed conformation is difficult or impossible to transcribe; transcription requires changes in chromatin structure..

• In an open conformation, the region is accessible to GTFs and RNA polymerase II and can therefore be transcribed.

• Changes in chromatin structure is controlled by chromatin remodeling.

• Changes include moving nucleosomes around.

• Replacing histone components.

• Two ways to modify chromatin structure:

• Modify histone tails

• Directly methylate cytosines

Nucleosome-Free Regions (NFR)

• Exist at the beginning and end of genes.
• Allow for access of RNA polymerase, a necessary step in transcriptional regulation.

Bacteria: Lac Operon

• Operon: a cluster of genes under the control of a single promoter. Example: lac operon in E. coli.

• The operon contains genes for lactose metabolism.

• lac operon is regulated by negative and positive control.

  • Negative Control: A repressor protein binds to the operator region preventing RNA polymerase from binding and transcribing the operon.
  • Positive Control: An activator protein, CAP (catabolite activator protein), binds to a CAP site.

• Additional Factors: Cyclic AMP (cAMP) is the small, effector molecule that controls the activity of CAP. cAMP levels are impacted by glucose levels:

• High glucose, low cAMP

• Low glucose, high cAMP

Regulatory Transcription Factors

• Proteins that bind to regulatory sequences in DNA and control gene expression
• Includes activators and repressors (negative and positive control in bacteria).

RNA Splicing

• Alternative splicing allows an organism to use the same gene to make different proteins at different stages of development.
• RNA binding proteins regulate translation of specific mRNAs.
• Example: iron regulation in mammals. The mRNA for ferritin, a protein that stores iron, is controlled by an Iron regulatory protein (IRP). The presence of iron in the cell stops the protein, and ferritin expression is turned on.

This quiz explores the mechanisms and significance of gene regulation in eukaryotic organisms. It covers topics such as gene expression, transcription factors, and developmental stages related to oxygen binding. Test your understanding of how gene regulation affects organismal biology.