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NUCLEUS
Chromatin
Gene regulation in Eukaryotes
Chromatin modification:
DNA
Today’s topics:
•  Control of transcription
Gene
RNA
–  Combinatorial control
–  Cell-specific transcription
Transcription
Exon
Intron
RNA processing
•  Chromatin remodeling
•  Post transcription gene
regulation
Transport to cytoplasm
Degradation
of mRNA
–  mRNA processing
–  Micro RNAs
–  Protein degradation
CYTOPLASM
Translation
Polypetide
28 November 2012
Chemical modification
Transport to cellular
destination
Active protein
Degradation of protein
Degraded protein
Control of Transcription in
Eukaryotes
Transcriptional synergy
•  Combinations of different enhancers affect the strength of
transcription
Promoter
Activators
DNA
Enhancer
Distal control
element
Activator proteins
bind to enhancer
sequences
Gene
Repressor proteins can inhibit transcription
TATA
box
General
transcription
factors
compete for binding site
DNA-bending
protein
Group of
mediator proteins
“hide” activator
RNA
polymerase II
Now transcription
can start
RNA
polymerase II
Transcription
initiation complex
interact with transcription factors at the
promoter
RNA synthesis
Fig. 18-9
1
Enhancer
Promoter
All cells have the
same genes, but
only certain
genes are
expressed in
each tissue
Albumin gene
Crystallin gene
GFP gene attached to cartilage-specific
control elements
Albumin gene
not expressed
Albumin gene
expressed
Liver
cell
Different activator
proteins in the
two cell types
Lens
cell
Crystallin gene
not expressed
Crystallin gene
expressed
Fig. 18-10
Signal
NUCLEUS
Chromatin
Nucleosomes
Chromatin modification
DNA
Gene available
for transcription
Gene
Transcription
RNA
Exon
Primary transcript
Intron
RNA processing
Tail
Cap
mRNA in nucleus
Transport to cytoplasm
CYTOPLASM
Fig. 18-6
Histone acetylation loosens DNA to
allow transcription
Unacetylated histones
Long-term control of transcription:
methylation
Acetylated histones
positive charge
(interacts with DNA)
acetylation
neutralizes charge
Acetyl group
Lysine
2
Signal
Alternative RNA splicing
NUCLEUS
Chromatin
modification:
DNA
Chromatin changes
Transcription
Gene
Transcription
RNA processing
RNA
Posttranscription
control of
gene
expression
mRNA
degradation
RNA processing
Translation
Protein processing
and degradation
Transport to cytoplasm
CYTOPLASM
Degradation
of mRNA
Exons
DNA
Translation
Polypetide
Primary
RNA
transcript
Activation
Active protein
RNA splicing
Degradation of protein
Degraded protein
or
mRNA
CYTOPLASM
Protein-coding RNA only accounts for
~1.5% of the human genome, but ~90% of
the genome appears to be transcribed…
What is it??
mRNA in cytoplasm
Degradation
of mRNA
Translation
Polypeptide
Protein activation
Degradation
Degradation
of protein
of protein
-rRNAs
-tRNAs
-snRNAs
-small regulatory RNAs
Active protein
Transport to cellular
destination
Cellular function
Fig. 18-6
Hairpin
miRNA and developmental complexity
miRNA
Hydrogen
bond
Dicer
miRNA
5! 3!
(a) Primary miRNA transcript
microRNAs
(miRNAs)
Technau 2008 Nature 455:1184
mRNA degraded
miRNAprotein
complex
Translation blocked
Fig. 18-13
3