BI2BMG4 MOLECULAR GENETCS - Eukaryotic Gene Expression Regulation

Eukaryotic Gene Expression Regulation

Overview

• Study source: "The Frustrated Gene: Origins of Eukaryotic Gene Expression" by Hiten D. Madhani, Cell, Volume 155, Issue 4, 744 - 749.

Key Features of Eukaryotic Gene Regulation

• Eukaryotic cells share some gene regulation features with bacteria but differ in key aspects:

  • Each gene is associated with its own promoter and transcribed separately.

  • DNA must unwind from histones before transcription can occur.

  • Transcription and translation are separated in time and space.

Chromatin Structure and Gene Expression

• DNase I Hypersensitivity:

  • Identifies sites with a more open chromatin configuration upstream of transcription start site.

• Histone Modifications:

  • Methylation: Addition of methyl groups to histone tails affects gene expression.

  • Acetylation: Addition of acetyl groups alters chromatin structure by neutralizing positive charges on lysine, increasing accessibility to transcription factors and facilitating transcription.

Role of Histones in Gene Regulation

• Acetylation of histones allows transcription factors to access DNA, leading to relaxed chromatin and active transcription processes.

• Example:

  • Flowering Locus C (FLC): Encodes a protein that represses flowering.

  • Flowering Locus D (FLD): Encodes a deacetylase that modifies histones influencing flowering in Arabidopsis.

Transcription Factors in Gene Regulation

• Gene expression is regulated by:

  • Transcriptional Activators: Stimulate transcription, interact directly with basal machinery.

  • Repressors: Inhibit transcription either by binding to operator sites or preventing translation.

  • Coactivators: Factors that connect activators to the basal transcription machinery but do not bind directly to DNA.

Machinery at the Promoter

• Core Promoter: Shortest DNA sequence necessary for transcription initiation, recognized by accessory proteins such as transcription factors.

Transcription Factors Classification

• General Transcription Factors: Required for transcription of all eukaryotic genes and necessary to form the initiation complex at promoters.

• Specific Transcription Factors: Act on individual genes, can bind far from the promoter due to 3D DNA structure.

Activation of Transcription Initiation

• Transcription relies on:

  • Mediator Complex: Communicates regulatory signals between transcription factors and RNA polymerase.

  • Enhancers: DNA sequences that stimulate transcription from a distance, can interact with various transcription factors.

  • Insulators: Block the effects of enhancers on adjacent genes.

Mechanism of Transcriptional Activation

• Activators bind specific base sequences and interact with transcriptional apparatus to enhance transcription rates.

• Architectural Proteins: Bend DNA, facilitating protein interactions essential for transcription.

Independent Domains in Activators

• DNA-Binding Domain: Determines specificity and brings activation domain close to the promoter.

• Transcriptional Activator Proteins Functions:

  • Bind to specific DNA sequences.

  • Interact with the transcription apparatus, influencing transcription rates.

Diverse Mechanisms of Coactivators

• Coactivators employ diverse functions:

  • Induce histone modifications (acetylation, methylation).

  • Facilitate DNA unwinding.

  • Recruit RNA polymerase II.

Summary of Key Concepts

• Every gene has a promoter that interacts with a basal transcriptional apparatus, while enhancer sequences can significantly impact transcription from a distance. Promoters can be constitutive or regulated, becoming active in response to specific stimuli.