Regulation of Gene Expression

Regulation of Gene Expression

Explanation of Differential Gene Expression

  • Core Idea: Two cells with the same genome can look and act differently due to variations in gene transcription.

    • Different genes are actively transcribed in different cells, leading to the production of varied sets of proteins.

    • Concept: This process is known as Differential Gene Expression.

Overview of Gene Regulation

  • Nature of Gene Regulation:

    • It is a tightly controlled and complex process involving:

    1. Different genes being transcribed to produce different RNA.

    2. Different proteins being produced as a result of these transcripts.

Student Learning Objectives (SLOs)

  • Predict the effect of chromatin remodeling on transcription.

  • Predict the effect of DNA methylation on transcription.

  • Contrast the roles of activator and repressor proteins in transcription and identify the DNA regions to which these proteins bind.

Chromatin Remodeling

  • Concept: Chromatin can exist in two states:

    1. Packed (Condensed): Inactive genes.

    2. Loose (Decondensed): Active genes.

  • Mechanism: Proteins add chemical tags to histone groups:

    • These tags relax the DNA, promoting decondensation.

    • Removal of these tags leads to DNA packing.

DNA Methylation

  • Definition: This process refers to the addition of chemical tags (specifically, methyl groups) to regions of DNA, particularly in GC-rich areas.

  • Function: Methylation can prevent transcription of a nearby gene, effectively turning it “off”.

    • It is an example of an epigenetic alteration that affects gene activation without changing the base sequence of the gene.

Transcription Activation

  • Process Overview:

    • Transcription activation requires more than RNA polymerase simply binding to the promoter region.

    • Promoter Binding: RNA polymerase recognizes and binds to the TATA box within the promoter, establishing basic machinery but not initiating transcription.

  • Role of Regulatory Proteins:

    • Regulatory Transcription Factors: Interact with RNA polymerase, including:

    • General transcription factors: Multiple factors that associate with RNA polymerase at the core machinery.

    • Activator Proteins: Bind to enhancer regions (which can be located adjacent or far from the promoter) to activate transcription.

    • Repressor Proteins: Bind to silencer regions to inhibit transcription.

Characteristics of Transcription Factors

  • Functionality:

    • Transcription factors recognize specific sequences within DNA and bind directly to these sequences.

Example of Gene Regulation: Kitl Gene

  • Function: The Kitl gene influences melanin production in a biological context.

  • Enhancer Binding: Activator proteins can bind to the enhancer region associated with the Kitl gene.

  • Data on Kitl mRNA Levels:

    • Depicted as a graph relative to control levels:

    • Y-axis: Kitl mRNA levels (normalized)

    • Control: Baseline levels compared to variations associated with different enhancer conditions labeled as “Blond” and “Dark”.

Control of Protein Production

  • SLO: Describe the role of microRNAs in mRNA stability and translation regulation.

RNA Interference (siRNA) & microRNAs (miRNA)

  • Overview:

    • Small RNA strands (siRNA and miRNA) bind to target mRNAs within a protein complex known as RISC (RNA-Induced Silencing Complex).

    • Implications:

    • Result in mRNA degradation

    • Block the translation of the mRNA, effectively preventing it from producing proteins.

Mutations

  • SLO: Identify various types of point mutations and predict their consequences.

Point Mutations

  • Definition: Change in the base sequence of DNA.

    • Most commonly arise from unrepaired errors during DNA replication before cell division.

    • Can also occur during DNA repair processes in response to mutagens.

    • The impact of mutations depends on their location within a gene.

Types of Point Mutations

  • Silent Mutation:

    • Definition: A change in the nucleotide sequence that does not alter the amino acid specified by a codon.

    • Example:

    • Original Sequence: TAT TGG CTA GTA CAT (encoding Tyr-Trp-Leu-Val-His)

    • Mutated Sequence (silent): TAC TGG CTA GTA CAT (still encoding Tyr-Trp-Leu-Val-His)

    • Consequence: Results in no change in phenotype; neutral concerning fitness.

  • Missense Mutation:

    • Definition: Change in nucleotide sequence that alters the amino acid specified by the codon.

    • Example:

    • Original Sequence: TAT TGG CTA GTA CAT (encoding Tyr-Trp-Leu-Val-His)

    • Mutated Sequence: TAT TGT CTA GTA CAT (encoding Tyr-Cys-Leu-Val-His)

    • Consequence: Can lead to a change in the protein’s primary structure, which may be beneficial, neutral, or deleterious.

  • Nonsense Mutation:

    • Definition: Change in the nucleotide sequence that produces an early stop codon.

    • Example:

    • Original Sequence: TAT TGG CTA GTA CAT (encoding Tyr-Trp-Leu-Val-His)

    • Mutated Sequence: TAT TGA CTA GTA CAT (leading to stop codon)

    • Consequence: Typically leads to truncated polypeptide synthesis; usually deleterious.

  • Frameshift Mutation:

    • Definition: Involves the addition or deletion of a nucleotide, altering the reading frame.

    • Example:

    • Original Sequence: TAT TGG CTA GTA CAT (encoding Tyr-Trp-Leu-Val-His)

    • Mutated Sequence: TAT TCG GCT AGT ACAT (shifted reading frame)

    • Consequence: Alters the meaning of all subsequent codons; almost always deleterious.