Gene Regulation
Gene Regulation
2007-2008
Points of control
• The control of gene expression
can occur at any step in the
pathway from gene to functional
protein
1. packing/unpacking DNA
2. transcription
3. mRNA processing
4. mRNA transport
5. translation
6. protein processing
7. protein degradation
1. DNA packing as gene control
• Degree of packing of DNA regulates transcription
– tightly wrapped around histones
• no transcription
• genes turned off heterochromatin
darker DNA (H) = tightly packed
euchromatin
lighter DNA (E) = loosely packed
H E
DNA methylation
• Methylation of DNA blocks transcription factors
– no transcription
genes turned off
– attachment of methyl groups (–CH3) to cytosine
• C = cytosine
– nearly permanent inactivation of genes
• ex. inactivated mammalian X chromosome = Barr body
2. Transcription initiation
• Control regions on DNA
– promoter
• nearby control sequence on DNA
• binding of RNA polymerase & transcription factors
• “base” rate of transcription
– enhancer
• distant control
sequences on DNA
• binding of activator
proteins
• “enhanced” rate (high level)
of transcription
Model for Enhancer action
Enhancer
Activator
Activator
Activator
Coactivator
B F E RNA polymerase II
A TFIID H
Core promoter
and initiation complex
Initiation Complex at Promoter Site binding site of RNA polymerase
3. Post-transcriptional control
• Alternative RNA splicing
– variable processing of exons creates a family of
proteins
6-7. Protein processing &
degradation
• Protein processing
– folding, cleaving, adding sugar groups,
targeting for transport
• Protein degradation
– ubiquitin tagging
– proteasome degradation
3 & 4. post-transcription
5 - mRNA processing
initiation of 4 - splicing
translation - 5’ cap & poly-A tail
mRNA
- breakdown by siRNA
processing
5. translation
- block start of
2
1 translation
initiation of
transcription 6 & 7. post-translation
- protein processing
- protein degradation
mRNA
mRNA splicing 4 protection
3