Genetic and Epigenetic Regulation

Chapter 17: Genetic and Epigenetic Regulation

  • All somatic cells are produced by the process of mitosis.

  • All somatic cells in an adult derive from a single fertilized egg (zygote).

  • The DNA in all somatic cells is the same.

  • Note: Although cells possess identical DNA, diverse expression leads to varied function and structure.

Gene Regulation Defined

  • Definition: Gene regulation refers to the mechanisms that cells utilize to control the expression of genes.

    • Significance: Allows unicellular organisms to adapt by creating specialized cells and making proteins only when necessary.

    • Energy Efficiency: By utilizing cellular specialists, energy expenditure is minimized.

Gene Regulation in Prokaryotes

Overview

  • Compared to eukaryotic regulation, prokaryotic gene regulation is simpler and involves different strategies of control.

Types of Genes in Bacteria

  • Gene states in bacteria:

    1. Constitutive Genes: Always active, such as those involved in glycolysis.

    2. Repressible Genes: Active but can be turned off, like those producing tryptophan.

    3. Inducible Genes: Normally inactive but can be turned on under specific conditions, e.g., genes breaking down lactose.

Mechanisms of Gene Regulation in Bacteria

  • Two Mechanisms:

    1. Negative Gene Regulation:

    • Active Repressors (aRep): Inhibit transcription.

    1. Positive Gene Regulation:

    • Active Activators (aCRP): Stimulate transcription.

Operons in Prokaryotes

  • Operon Components:

    • Promoter: Region where RNA polymerase initiates transcription.

    • Operator: Site where repressor or activator proteins bind to regulate transcription/ turn it off

    • Structural Genes: Genes that are transcribed into mRNA and subsequently translated into proteins.

Operon Regulation

  • Regulator Genes:

    • Not part of the operon but essential for its control.

    • Produce:

      • Activators: Facilitate the turning ON of operons.

      • Repressors: Facilitate the turning OFF of operons.

  • **Negative Gene Regulation Mechanism: **

    • Active Repressor (aRep): Binds to operator blocking RNA polymerase.

Positive Gene Regulation Mechanism

  • Active Activator (aCRP): Binds to operator, enabling RNA polymerase attachment.

  • Inactive Activator (iCRP): Cannot bind to operator, hence transcription is not initiated.

The Lactose Operon (lac operon)

  • Function: Genes facilitate the breakdown of lactose.

  • Condition Requirements: Only expressed when lactose is present and glucose is low (to conserve energy).

Regulation Without Lactose

  • Mechanism:

    • Active Repressor (aRep) binds to the operator, preventing transcription.

Regulation With Lactose

  • Mechanism:

    • Lactose binds to aRep, converting it to iRep, allowing RNA polymerase to transcribe the genes.

  • Transcription Level: Low transcription observed due to partial engagement.

Influence of Glucose on the lac Operon
Activator Protein (CRP) in lac Operon Regulation

  • Inactive Form: iCRP.

  • Active Form: aCRP generated through cAMP interaction with iCRP.

  • Condition for Activation: Absence of glucose results in aCRP activation leading to transcription initiation.

Summary of lac Operon Activation

  • Key Requirements for Full Activation of lac Operon:

    1. Inactive Repressor (iRep) is present (requires lactose).

    2. Active Activator (aCRP) is present (requires cAMP with low glucose conditions).

Gene Regulation in Eukaryotes

Mechanisms of Regulation

  1. Modification of Histones and DNA Bases

  2. Transcription Control

  3. RNA Processing

  4. RNA Lifespan

  5. Post-Translational Modifications

Chromatin Structure and Remodeling

  • Chromatin Composition: Contains DNA, RNA, and histone proteins.

Histone Modification and Epigenetics

  • Acetylation of Histones:

    • Addition of acetyl groups results in relaxed chromatin, promoting gene expression.

  • Methylation of Cytosines:

    • Involves adding methyl groups (-CH3) to cytosine nucleotides leading to chromatin condensation and gene silencing.

  • Epigenetic Effects:

    • Modification of chromatin components influencing gene expression without altering the DNA sequence itself.

Transcriptional Regulation in Eukaryotes

  • Process Overview:

    • Transcription Factors:

      • Bind to the gene's promoter region.

      • Recruit additional components necessary for RNA polymerase binding.

Enhancers and Combinatorial Control

  • Enhancer Regions:

    • Additional binding sites for regulatory factors, influencing transcriptional outcomes based on combinations of factors.

RNA Processing Regulation

  • Alternative Splicing:

    • Different mRNA variants produced from the same pre-mRNA may lead to proteins with various functions based on cell type.

  • RNA Editing:

    • Modifications post-transcription can lead to altered amino acid coding after translation.

mRNA Lifespan and Regulation

  • Variability:

    • mRNA lifespan can range from minutes to days/weeks.

    • Longer lifespan correlates with increased protein synthesis.

      • siRNA (Small Interfering RNA)

      • miRNA (Micro RNA)

Post-Translational Regulation

  • Modifications After Translation:

    • Potential alterations include cleavage, sugar addition, and phosphorylation, altering protein structure and function.

  • Functional Implications:

    • Modifications affect protein shape, thus influencing its functionality and interactions within the cell.