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:

    1. Cell differentiation: Allowing various cell types with different functions to arise from a single type of cell.

    2. Developmental stages of multicellular organisms: Enables progression from zygote to embryo to fetus to juvenile to adult.

    3. 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

  1. Enzymatic Degradation of mRNA: Influences how much protein is synthesized; timing is crucial.

  2. Regulation of Translation Initiation: Proteins can prevent translation if the resultant protein is not needed.

  3. 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.