IS IT NATURE OR NURTURE? Regulation of Gene Expression

IS IT NATURE OR NURTURE?

Lecture 6: Regulation of Gene Expression

Overview of Gene Expression

• The human genome:

  • Comprises 20,000+ genes.

  • Genes are regions of DNA that encode for proteins, with lengths varying from 500 to >2 million nucleotides.

  • Most of the human DNA does not encode proteins.

• Gene Expression:

  • Refers to when a gene is actively transcribed—also called the gene being ‘on’.

  • After transcription, the mRNA must be translated to produce protein.

• Cellular Composition:

  • All cells in the human body contain the entire genome—meaning all cells share the same genes and alleles.

Cellular Differentiation

• The variance in selective functions and appearances of cells results from the presence of distinct proteins produced by each cell type.

• The specific pattern of proteins produced, for instance in red blood cells vs neurons, depends on the regulation of gene expression.

Course Objectives

• Understand the concept and significance of gene regulation for cells and organisms.

• Identify and describe parts of genes and their respective roles, including regulatory vs coding regions.

Understanding Gene Regulation

• Necessity of Gene Regulation:

  • Cells do not require every protein at all times, making it energetically prudent to regulate protein synthesis.

  • Gene regulation involves processes that manage when and where a gene is expressed and the quantity of transcription, affecting protein production.

  • A significant segment of the genome includes components for gene regulation.

Gene Expression Patterns

• Expression means actively synthesizing protein.

• Housekeeping Genes:

  • These are genes whose products are needed consistently across all cells, hence are constitutively expressed.

  • Example: Genes involved in energy production and transport of molecules.

• Regulated Genes:

  • Expression is controlled based on specific signals or conditions, such as immune genes activated in response to infection.

Differential Regulation in Cells

• Genes are expressed differently in various cell types based on environmental changes.

  • Genes can be turned ‘on’ (expressed) or ‘off’ (not expressed), leading to diverse cellular functionalities.

• Such regulation distinguishes functionally different cell types (e.g., heart cells, nerve cells, liver cells).

Structure of Genes

• Parts of a Gene:

  • Non-coding region (Regulatory):

  • Contains the promoter, which controls when, where, and how much gene is transcribed.

  • Coding region:

  • Contains the start codon (AUG) where translation commences.

  • Exons are regions that directly code for amino acids and are expressed.

  • Introns are transcribed but not translated, situated between exons.

  • The stop codon marks the end of translation.

Gene Expression Regulation via Promoters

• Promoter is a DNA sequence found within the regulatory region of a gene.

• RNA Polymerase binds to the promoter to initiate transcription.

  • The term polymerase signifies an enzyme that links building blocks (nucleotides) into larger DNA/RNA molecules.

• Transcription Factors:

  • Proteins that bind to promoters and serve as either activators (turn transcription on) or repressors (turn transcription off).

  • Transcription factors respond to various cellular signals, influencing gene expression.

Example of a Transcription Factor

• Steroids:

  • Small hydrophobic molecules that diffuse through cell membranes, requiring no energy.

  • Steroids lead to the transcription of specific genes, such as testosterone, which influences muscle mass development.

RNA Transcription and Processing

• Transcription involves making RNA from a DNA template, resulting in a primary transcript that is not yet mature mRNA.

• Primary RNA Transcripts undergo modifications:

  • 5’ Cap and Poly-A Tail are added to facilitate exit from the nucleus and protect the RNA from degradation.

  • Splicing occurs, removing introns to produce mature mRNA which is ultimately translated.

• Splicing of introns allows for multiple proteins to arise from a single gene due to the removal or inclusion of different exons.

Regulation of Gene Expression Levels

• Gene Regulation Occurs at Several Levels:

  • Transcriptional Control: Determines if a gene is transcribed into mRNA.

  • RNA Processing Control: Manages intron removal and RNA alterations.

  • RNA Transport Control: Oversees if mRNA exits the nucleus for translation.

  • Translation Control: Regulates the translation process and the quantity of protein synthesized per mRNA.

Introduction to Epigenetics

• Epigenetics provides another layer of gene expression regulation.

• Definition of Epigenetics:

  • Epigenetics describes heritable alternative gene activity states that do not arise from changes in the DNA sequence.

  • Influenced by environmental factors such as diet and exercise.

• In the context of nature vs nurture, epigenetics illustrates how the environment modifies the expression of genetic potential.

DNA Methylation and Its Impact

• Methylation of DNA:

  • Methylation pertains to adding a methyl (CH3) group to DNA bases, affecting gene activity without altering the nucleotide sequence.

• Methylation can greatly influence gene expression.

• Specific examples include cytosine methylation primarily in regions with high G and C content affecting gene activity:

  • High levels of methylation tend to turn genes off.

Implications of Methylation

• The structural alterations due to methylation can hinder transcription factor binding, rendering the associated genes inaccessible (off).

• Environmental factors, like exposure to chemicals, can permanently alter methylation patterns through generations, impacting health in descendants.

• Examples of Epigenetic Effects in Animals:

  • Vinclozolin: A fungicide that causes lasting epigenetic alterations potentially leading to fertility issues through generations.

• Effects observed in humans are harder to study but include correlations like:

  • Grandmaternal smoking linked to asthma in grandchildren.

  • Grandchildren’s birth weight influenced by grandparents’ socio-economic statuses.

Conclusion on Epigenetic Changes

• Chemical modifications of cytosine and other DNA structures significantly alter how genes are expressed without mutations.

• Epigenetic changes can create substantial phenotypic differences, impacting gene regulation throughout an organism's life.

• Inheritance of these epigenetic changes poses challenges in research and remains a topic of debate within the scientific community.