Transcript Eukaryotic Gene Expression

Eukaryotic Gene Expression
Introduction
• Every cell in a multi-cellular eukaryote
does not express all its genes, all the
time (usually only 3-5%)
– Long-term control of gene expression in
tissue = differentiation
• How to prevent expression?
– Regulation at transcription
– Regulation after transcription
Chromatin Regulation
• Chromatin remodeling allows
transcription
– Chromatin = DNA + proteins
– Chromatin coiled around histones =
nucleosomes
– Allows DNA to be packed into nucleus, but
also physically regulates expression by
making regions ‘available’ or not
Chromatin Regulation Con’t
• Chromatin regulation can be small-scale
(gene) or large scale (chromosome)
– Non-expressed = heterochromatin
(condensed)
– Expressed = euchromatin (relaxed)
• Example of whole-chromosome
regulation: Barr bodies
Gene Amplification
• To increase gene expression, make
temporary copies of a gene, aka gene
amplification
• Can happen in certain tissues or stages
of development
– Embryos require massive volumes of rRNA
(to make ribosomes); in early development
there are a million+ extra rRNA genes (not
able to replicate) present in nucleus
Transcription Regulation
• What we know from prokaryotes:
– Several related genes can be transcribed together
(ie. lac operon)
– Need RNA Polymerase to recognize a promoter
region
• Why eukaryotes are different:
– Genes are nearly always transcribed individually
– 3 RNA Polymerases occur, requiring multiple
proteins to initiate transcription
Transcription Regulation Con’t
• Typical prokaryotic promoter:
recognition sequence + TATA box ->
RNA Polymerase attachment ->
transcription
• Typical eukaryotic promoter: recognition
sequence + TATA box + transcription
factors -> RNA Polymerase II
attachment -> transcription
Transcription Regulation Con’t
• RNA polymerase interacts w/promoter,
regulator sequences, & enhancer
sequences to begin transcription
– Regulator proteins bind to regulator sequences to
activate transcription
• Found prior to promoter
– Enhancer sequences bind activator proteins
• Typically far from the gene
• Silencer sequences stop transcription if they
bind with repressor proteins
Transcription Regulation Con’t
• If eukaryotic genes
are typically ‘alone’,
how to regulate
expression of
several?
• Conserve regulatory
sequences!
Now, Can You:
• Explain why gene expression control is
necessary in a eukaryotic cell?
• Describe how expression is regulated in
before & during transcription?
• Tell me what differentiation is?
Euchromatin? A silencer sequence?
• Explain how gene expression regulation
is different in eukaryotes/prokaryotes?
Post-Transcription Regulation
• Have mRNA variation
– Alternative splicing: shuffling exons
– Allows various proteins to be produced in different
tissues from the same gene
• Change the lifespan of mRNA
– Produce micro RNA that will damage mRNA,
preventing translation
• Edit RNA & change the polypeptide produced
– Insert or alter the genetic code
Translation Regulation
• mRNA present in cytosol does not
necessarily get translated into proteins
– Control the rate of translation to regulate
gene expression
• How?
– Modify the 5’ cap
– Feedback regulation (build up of products
= less translation)
Translation Regulation Con’t
• Modify the
lifespan of
proteins:
– Attach
ubiquitin =
target for
breakdown via
proteasome
(woodchipper)
So…
• What are the ways that a cell can
regulate gene expression AFTER
transcription?
• How can the process of RNA splicing
allow one pre-mRNA to produce 5
different proteins in 5 different tissues?
• And…
• Can you accurately fill in this table?