Ch 11 Gene Control
Gene Regulation Overview
All cells in an organism contain the same DNA.
Only a small number of genes are expressed at any given time.
Gene Regulation: The processes that determine which genes are expressed and at what rate in a given cell.
Importance of Gene Regulation
Gene regulation provides:
Cell differentiation: Allowing various cell types with different functions to arise from a single type of cell.
Developmental stages of multicellular organisms: Enables progression from zygote to embryo to fetus to juvenile to adult.
Adaptation of cells: Cells can synthesize different proteins as needed to respond to changing environmental conditions.
Prokaryotic Regulation: The Operon Model
The Operon Model was the first mechanism of gene regulation discovered in bacteria (specifically E. coli) in the 1950s.
An operon is a region of DNA that includes:
Promoter: A sequence signaling to RNA polymerase where to bind and start transcription.
Operator: A short DNA segment following the promoter where an active repressor protein can bind, determining if RNA polymerase can attach to the promoter.
Structural Genes: One to several genes that code for enzymes in a metabolic pathway, which can be expressed simultaneously.
Regulatory Gene: Codes for the repressor but is not part of the operon.
Function and Mechanism of the Operon Model
The primary purpose of an operon is to regulate transcription, which is the first step in gene expression; without transcription, there can be no translation and thus no protein produced.
The Lac Operon
Lac Operon: Found in E. coli, regulates genes that produce enzymes for lactose breakdown.
Energy Efficiency: E. coli only produces lactose-utilizing enzymes when lactose is present, and glucose is absent to avoid wasting energy.
Inducible Operon: Typically off but can be induced to turn on.
Lac Operon Operation
When glucose is available and lactose is absent:
Repressor protein attaches to the operator.
Lac operon expression is “off”.
When glucose is limited and lactose is present:
Lactose binds to the repressor, preventing it from attaching to the operator.
Induces lac operon (turns it “on”).
RNA polymerase binds to the promoter, and lac operon genes are expressed.
Three enzymes required for lactose utilization are produced.
Variants of Operons: Inducible vs Repressible
Inducible Operons: Usually “off” until a gene is induced to turn “on”. This may involve a repressor that needs to be removed or may require an activator protein to turn it on.
Repressible Operons: Usually “on” but can be turned off when a specific molecule is present. For example, E. coli can make tryptophan but stops production when enough is available in its environment to avoid waste.
Eukaryotic Gene Regulation
All organisms utilize gene regulation, though eukaryotic mechanisms are more complex than those in prokaryotes.
Eukaryotes have additional methods for regulating genes and achieving gene differentiation.
Effects of Gene Regulation on Cell Differentiation
Different cell types (muscle, nerve, skin cells) possess the same DNA but express different genes, leading to cell specialization.
DNA Packing and Structure
Chromatin: DNA form during interphase, not tightly wound.
Chromosomes: Tightly wound DNA during mitosis.
Specific DNA regions may remain tightly wound during interphase, preventing transcription (gene “off”).
DNA Structural Levels
Structure of DNA includes:
Double Helix: 2-nm diameter.
Nucleosome: 10-nm fiber, bead-like structure of histones.
Tight Helical Fiber: 30-nm fiber.
Looped Domain: 300-nm fiber.
RNA Splicing
Eukaryotic RNA can undergo variety forms of splicing.
Approximately 21,000 human genes can produce more than 100,000 polypeptides due to alternative splicing.
Post-Transcriptional Regulation
Enzymatic Degradation of mRNA: Influences how much protein is synthesized; timing is crucial.
Regulation of Translation Initiation: Proteins can prevent translation if the resultant protein is not needed.
Post-Translational Modifications: Polypeptides typically need alterations (e.g., insulin processing) to become functional.
Epigenetic Factors in Gene Regulation
Transposons
Also known as “jumping genes”, are repetitive DNA sequences that can transfer between chromosomes, enhancing genetic diversity, but may disrupt genes if they insert into coding regions.
Discovered by geneticist Barbara McClintock.
Epigenetic Inheritance
Describes the inheritance of traits not related to changes in the nucleotide sequence.
Examples include the modification of histones and DNA methylation.
Chemical Modifications to Histones
Histone modifications involve adding functional groups:
Methyl groups (CH3): Cause tighter winding; reduces transcription.
Acetyl groups (COCH3): Cause looser winding; increases transcription.
Methylation of DNA
Addition of methyl groups (CH3) to DNA generally inhibits gene transcription. Once methylated, DNA tends to maintain this status across generations.
X Inactivation
Female mammals have two X chromosomes but do not express double the X-linked proteins compared to males.
One X chromosome in each somatic cell develops into a highly compacted structure known as a Barr Body, effectively inactivating it.
X inactivation occurs early in embryonic development, with random X chromosome selection; all resulting daughter cells maintain the same inactivated X chromosome.
Heterozygosity in females can result in cells expressing different alleles due to X inactivation.