Ch.8 Transcriptional Control of Gene Expression

Chapter 8: Transcriptional Control of Eukaryotic Gene Expression

Overview

  • Single-cell yeast and multi-cellular organisms exhibit different gene expression responses to environmental factors.

  • Transcription rates, particularly initiation rates, are central to gene expression regulation in higher eukaryotes.

  • Chromatin structure (including histone proteins and nucleosomes) significantly influences transcription control.

Measurement of Transcription Rates

  • Transcription rates are primarily quantified through classic run-on experiments, indicating that protein concentrations are regulated by these rates.

  • Techniques involve radioactively labeling nascent RNA and hybridization to measure transcription activity.

Cis-Regulatory Elements

  • Eukaryotic cis-regulatory elements can be located both proximally and distally to transcription start sites, affecting gene expression.

  • Comparative genomics can uncover conserved elements essential for developmental processes and gene regulation across species.

RNA Polymerases in Eukaryotes

  • Three main RNA polymerases exist with specific RNA products:

    • RNA Pol I: Pre-rRNA

    • RNA Pol II: mRNA, snRNA, siRNA, miRNA

    • RNA Pol III: tRNA, 5S rRNA

  • Each polymerase has distinct sensitivities to inhibitors such as a-amanitin.

General Transcription Factors (GTFs)

  • GTFs, including TFIID, recruit RNA Pol II to transcription start sites and facilitate the assembly of the pre-initiation complex (PIC).

  • TBP (TATA Binding Protein) plays a crucial role in promoter recognition and DNA bending.

Transcription Initiation and Regulation

  • Transition from closed to open PIC is essential for transcription initiation, often facilitated by phosphorylation of Pol II CTD (Carboxy Terminal Domain).

  • Chromatin remodeling and histone modifications (acetylation and methylation) are key for regulating access to transcriptional machinery.

Activators and Repressors

  • Activators contain distinct domains for DNA binding and transcription activation, while repressors block transcription through various mechanisms (competitive binding, interaction with activators, or GTFs).

  • Most transcription factors display modular designs that facilitate varied regulatory roles.

Epigenetics in Gene Regulation

  • Epigenetic modifications (e.g., DNA methylation and histone modifications) impact gene expression patterns without altering DNA sequences.

  • Long noncoding RNAs contribute to both activation and repression of gene expression, playing significant roles in development and other processes.

Transcription Mechanism of RNA Polymerases

  • RNA Pol I and III transcribe rRNA and small RNAs, respectively, employing specific promoter elements and factor interactions for transcription initiation.

  • TBP is a common component across all polymerases, suggesting evolutionary conservation and functional interdependence.