Eukaryotic Gene Regulation
EUKARYOTIC GENE REGULATION................................................................................................................... 1
INTRODUCTION............................................................................................................................................ 2
GENERAL CONCEPTS...............................................................................................................................................2
EUKARYOTIC VS PROKARYOTIC.................................................................................................................................2
GENE STRUCTURE..................................................................................................................................................2
Cis-acting elements:........................................................................................................................................3
LEVELS OF REGULATION..........................................................................................................................................3
CONTROL OF TRANSCRIPTIONAL INITIATION................................................................................................. 3
POLYMERASES.......................................................................................................................................................3
RNA Pol II Transcription..................................................................................................................................3
BASAL FACTORS.................................................................................................................................................... 4
TRANSCRIPTION FACTORS........................................................................................................................................4
Transcription Factor Domains.........................................................................................................................5
TF activity is tightly controlled:.......................................................................................................................5
INTEGRATION OF CELLULAR INFORMATION..................................................................................................................5
REPORTER ASSAYS.................................................................................................................................................5
CHROMATIN STRUCTURE.............................................................................................................................. 6
CHROMATIN REGULATION OF TRANSCRIPTION.............................................................................................................6
HISTONE MODIFICATION......................................................................................................................................... 6
Lysine acetylation:..........................................................................................................................................6
CHROMATIN REMODELING (EPIGENETIC EFFECTS).........................................................................................................7
POST-TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION.......................................................................7
(MRNA) SPLICING.................................................................................................................................................7
SIRNA.................................................................................................................................................................7
MIRNA............................................................................................................................................................... 8
miRNA processing:..........................................................................................................................................8
MIRNA & SIRNA DOWN-REGULATION ON GENE EXPRESSION OF TARGET GENES:...............................................................8
RNA EDITING....................................................................................................................................................... 8
RNA STABILITY......................................................................................................................................................8
TRANSLATIONAL REGULATION...................................................................................................................................8
POST-TRANSLATIONAL REGULATION...........................................................................................................................9
1
, Eukaryotic Gene Regulation
Introduction
General Concepts
- Eukaryotes use complex sets of interactions
o Maintenance of homeostasis and response to environmental, physiological
and developmental signals in multicellular eukaryotes:
Genes are turned on or off in the right place and time (Spatial and
temporal regulation)
Differentiation and precise positioning of tissues and organs during
embryonic development
Coordination and communication between multiple cells and organs
o Regulated interactions of large networks of genes
o Each gene has multiple points of regulation, responding to multiple signals.
-
Eukaryotic Vs Prokaryotic
- Eukaryotes have much greater levels of complexity for controlling of gene expression
than prokaryotes:
o Eukaryotic genomes are larger than prokaryotic genomes
o Chromatin structure in eukaryotes makes DNA unavailable to transcription
machinery
o Additional RNA processing events occur in eukaryotes
o In eukaryotes, transcription takes place in the nucleus and translation takes
place in the cytoplasm
Gene structure
- Exons: sequences that end up in mature mRNA and reach the cytoplasm
- Introns: segments of gene that are in the primary transcript but are not included in
the mRNA and are removed during splicing.
- Cap site: beginning of first exon
- Poly (A) site: end of last exon
o Sequence that causes synthesis of multiple A nucelotide sequences at the
end of mRNA transcription
- Control regions – can be close to first exon or far away.
- Promoter-proximal elements:
- Downstream =. 3’ direction
- Upstream, = 5’ direction
- Enhancers can be present
- TATA box = ±-30 bp (In mammals) in 5’ direction; directs where RNA polymerase will
assemble.
2
EUKARYOTIC GENE REGULATION................................................................................................................... 1
INTRODUCTION............................................................................................................................................ 2
GENERAL CONCEPTS...............................................................................................................................................2
EUKARYOTIC VS PROKARYOTIC.................................................................................................................................2
GENE STRUCTURE..................................................................................................................................................2
Cis-acting elements:........................................................................................................................................3
LEVELS OF REGULATION..........................................................................................................................................3
CONTROL OF TRANSCRIPTIONAL INITIATION................................................................................................. 3
POLYMERASES.......................................................................................................................................................3
RNA Pol II Transcription..................................................................................................................................3
BASAL FACTORS.................................................................................................................................................... 4
TRANSCRIPTION FACTORS........................................................................................................................................4
Transcription Factor Domains.........................................................................................................................5
TF activity is tightly controlled:.......................................................................................................................5
INTEGRATION OF CELLULAR INFORMATION..................................................................................................................5
REPORTER ASSAYS.................................................................................................................................................5
CHROMATIN STRUCTURE.............................................................................................................................. 6
CHROMATIN REGULATION OF TRANSCRIPTION.............................................................................................................6
HISTONE MODIFICATION......................................................................................................................................... 6
Lysine acetylation:..........................................................................................................................................6
CHROMATIN REMODELING (EPIGENETIC EFFECTS).........................................................................................................7
POST-TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION.......................................................................7
(MRNA) SPLICING.................................................................................................................................................7
SIRNA.................................................................................................................................................................7
MIRNA............................................................................................................................................................... 8
miRNA processing:..........................................................................................................................................8
MIRNA & SIRNA DOWN-REGULATION ON GENE EXPRESSION OF TARGET GENES:...............................................................8
RNA EDITING....................................................................................................................................................... 8
RNA STABILITY......................................................................................................................................................8
TRANSLATIONAL REGULATION...................................................................................................................................8
POST-TRANSLATIONAL REGULATION...........................................................................................................................9
1
, Eukaryotic Gene Regulation
Introduction
General Concepts
- Eukaryotes use complex sets of interactions
o Maintenance of homeostasis and response to environmental, physiological
and developmental signals in multicellular eukaryotes:
Genes are turned on or off in the right place and time (Spatial and
temporal regulation)
Differentiation and precise positioning of tissues and organs during
embryonic development
Coordination and communication between multiple cells and organs
o Regulated interactions of large networks of genes
o Each gene has multiple points of regulation, responding to multiple signals.
-
Eukaryotic Vs Prokaryotic
- Eukaryotes have much greater levels of complexity for controlling of gene expression
than prokaryotes:
o Eukaryotic genomes are larger than prokaryotic genomes
o Chromatin structure in eukaryotes makes DNA unavailable to transcription
machinery
o Additional RNA processing events occur in eukaryotes
o In eukaryotes, transcription takes place in the nucleus and translation takes
place in the cytoplasm
Gene structure
- Exons: sequences that end up in mature mRNA and reach the cytoplasm
- Introns: segments of gene that are in the primary transcript but are not included in
the mRNA and are removed during splicing.
- Cap site: beginning of first exon
- Poly (A) site: end of last exon
o Sequence that causes synthesis of multiple A nucelotide sequences at the
end of mRNA transcription
- Control regions – can be close to first exon or far away.
- Promoter-proximal elements:
- Downstream =. 3’ direction
- Upstream, = 5’ direction
- Enhancers can be present
- TATA box = ±-30 bp (In mammals) in 5’ direction; directs where RNA polymerase will
assemble.
2
