Gene Regulation 5 - Regulation of eukaryotic gene expression - Transcriptional regulation Flashcards
Learning Outcomes
Students will be able to
➢ explain the terms housekeeping, constitutive, facultative, induced and repressed genes and how this
relates to gene expression in different cell types.
➢ list the type of genes transcribed by RNA polymerases in prokaryotic and eukaryotic cells.
➢ compare the general structure of prokaryotic and eukaryotic protein coding genes.
➢ describe different promoter elements of eukaryotic, RNA polymerase II transcribed genes.
➢ describe different types of transcription factors and how they regulate the expression of RNA
polymerase II transcribed genes.
➢ explain how epigenetic modifications and chromatin remodeling contribute to the regulation of gene
expression and development.
Regulation of gene expression in eukaryotes
- Control of gene expression in eukaryotes occurs at several
levels:
1) Packing or unpacking DNA
2) Transcription
3) mRNA processing
4) mRNA export
5) Translation
6) Post-translation protein modification
7) Protein degradation
Genes are expressed at different levels
- Only subsets of genes are expressed in a cell type ➔ expression levels of genes varies from one cell type to another.
– depends on cell type and internal or external conditions of the cell, e.g. changes in a cell’s environments or cell cycle
stage. - Expression of all genes requires regulatory elements. These are DNA sequence motifs in promoters (cis-acting elements)
and transcription factors (trans-acting factors). These vary between genes.
Housekeeping Genes are expressed in all cell types
- Some genes are expressed in all cells: housekeeping genes (here gene B).
– can be constitutive expressed genes = transcribed continually.
– can be expressed at a relatively constant levels or have varying expression levels.
– required for the maintenance of basic cellular functions, vital for survival. - Examples: RNA polymerase, DNA repair enzymes, structural proteins of
chromosomes, enzymes of basic metabolic processes.
Facultative Genes are expressed when the gene product is needed
- A specific cell only expresses a subset of the genes in its genome.
- Facultative genes ➔ only expressed when required (here gene A and C)
– Inducible and repressible genes ➔ expression is responsive to changing internal or external conditions, they may
respond to environmental change or they may be dependent on the cell cycle.
Eukaryotes use three different RNA polymerases
for different gene types
Prokaryotes:
* have only one RNA polymerase, transcribes all
prokaryotic genes
* Can initiate transcription on its own
– The RNA polymerase sigma subunit positions the
polymerase at the promoter
Eukaryotic protein encoding genes are more complex than
Prokaryotic genes
Eukaryotes:
* RNA polymerase I: ribosomal RNA genes: 5.8S rRNA, 18S rRNA & 28S rRNA genes
* RNA polymerase II: all protein-coding genes ➔ mRNAs
* small nucleolar RNA genes: guide chemical modifications of RNAs such as
tRNAs; some small nuclear RNA genes: help in mRNA splicing; microRNA
genes: involved in the regulation of gene expression
* RNA polymerase III: tRNA genes, 5S rRNA gene, some snRNA genes, other small
RNA genes
* Each eukaryotic RNA polymerase requires different promoter elements and
different transcription factors
Prokaryotic genes:
▪ Often polycistronic = encode for
more than one protein
▪ Organised in operons
▪ few shared, simple regulatory
elements (promoter, operator)
Eukaryotic genes:
▪ Usually monocistronic =
encode for one protein
▪ Most have introns
▪ Very complex promoters:
reflect complexity of
organism with many cell
types, many functions
Eukaryotic promoter of RNA polymerase II transcribed genes
are more complex than prokaryotic promoters
Cell specific Regulation of transcription requires a large variety of
Transcription Factors (TFs)
Two main categories of eukaryotic transcription factors:
* General TFs: bind to core promoter elements, help RNA polymerase to initiate transcription
* Cell or tissue specific TFs: transcription regulators that bind to promoter proximal elements or to distal
promoter elements, DNA sequence specific, modulate expression levels in response to signals.
Eukaryotic promoter of RNA polymerase II transcribed genes
are more complex than prokaryotic promoters
- Core Promoter: determine the transcription start site & direct binding of RNA pol II. Contain TATA box in rapidly
transcribed genes - Transcription control regions: mediate cell type specific expression and activate transcription. Short (6-10 bp) DNA
sequence elements that bind activating transcription factor proteins.
– Promoter proximal elements: close to transcriptional start site (within 200 bp)
– Distal Promoter elements: Enhancer or Repressor Elements: far from transcriptional start site (up to 50,000 bp)
General Transcription Factors position
RNA polymerase II at the Core Promoter
- General Transcription Factors have a similar
role in eukaryotic transcription as the sigma
factor has in bacterial transcription. - They assemble sequentially at the core
promoter of protein encoding genes:
– The TBP (TATA Binding Protein), a subunit
of TFIID binds to the TATA box in the core
promoter
– TFIIB, TFIIE and TFIIH assemble then
sequentially
– TFIIF positions the RNA polymerase II at the
transcription start site - Preinitiation complex
– TFIIH uses energy (ATP) to pull apart the
DNA double helix, exposing the template
strand ➔ allows RNA pol II to begin
transcription
Some transcription factors can be activated
DNA methylation is both dynamic and essential for normal development
DNA methylation patterns can be inherited by daughter cells
