Download Eukaryotic Gene Regulation

Eukaryotic Gene
Regulation
Chromatin Structure
DNA & protein
1) Nucleosomes
DNA &
histones
(proteins)
DNA wrapped
around 8-piece
histone bead
Chromatin Structure
2) 30-nm chromatin fiber
3) Looped domains
Fiber loops around
scaffold of nonhistone
proteins
4) Metaphase chromosome
Further folding & coiling
to compact
Chromatin Structure
In interphase, compacted chromatin:
heterochromatin (not transcribed –
proteins can’t reach the DNA)
Non-compacted: euchromatin (is
transcribed)
Genomic Organization
Gene Rearrangement
Loss or shuffling of genome
Change loci of genes in somatic cells
Transposons
If it “jumps” into middle of a
coding sequence, it stops normal
function
Itself can be activated if near active
promotor
Genomic Organization
10% of human genome, but many are
retrotransposons
Move by means of RNA intermediate
& reverse transcriptase
Process like retroviruses
Control of Gene Expression
Cellular Differentiation
Become specialized for a function
Only fraction of genes turned on (3-5%)
Regulated at transcription by DNAbinding proteins that receive internal &
external signals
Control of Gene Expression
Chemical modification of chromatin
also regulates transcription
1)DNA methylation
Attachment of -CH3 groups to
DNA bases (cytosine) after DNA
synthesis
Inactive DNA is highly methylated
(removing can possibly activate
genes)
Control of Gene Expression
Once methylated, tend to stay that way
through cell divisions
The pattern is passed on – form of
genomic imprinting (it permanently turns
off maternal or paternal allele)
Control of Gene Expression
2)Histone Acetylation
Attachment of acetyl groups (-COCH3)
to amino acids of histones
Changes their shape – grip DNA less
Easier to transcribe
that section of DNA
Control of Gene Expression
3) Control elements
Noncoding DNA regulating
transcription
Proximal control elements –
promotor
Control of Gene Expression
Distal control elements (farther away) –
enhancers
Causes DNA to bend so transcription
factors (activators) bound to enhancers
can contact proteins of TIC of promoter
Repressors bind to control elements
known as silencers (much less common)
Control of Gene Expression
Coordination
Need to turn genes of related function on
or off at same time
No operons like prokaryotes
Each gene has own promotor, so how to
coordinate?
Copies of transcription factors associate
with specific control elements of related
genes – they activate by same signal
(through signal-transduction pathways),
bind, & transcribe simultaneously
Control of Gene Expression
4) mRNA Degredation
5) Translation initiation
Blocked by proteins that bind to 5’ end of
mRNA so ribosome cannot attach
Control of Gene Expression
6) Protein processing & degradation
After translation
During modification or transport of
protein
FYI…To destruct protein, it is
marked with a protein ‘tag’
(ubiquitin); proteasomes recognize
this & degrade the protein
Cancer
Cancer-causing genes: oncogenes
From retroviruses
Normal gene – proto-oncogene
Normal becomes cancer in three
ways:
Movement of DNA within genome
Amplification of proto-oncogene
Point mutation of proto-oncogene
Cancer
Tumor-suppressor genes
Prevent uncontrolled growth
If damaged, cancer could result
Typical jobs:
repair damaged DNA to prevent
improper accumulation
Control cell anchorage (absent in
cancer)
Cancer
Genes often involved:
1) ras – mutated in 50% of cancers
Uses signal-transduction pathway
Ras is a G protein – end result –
synthesis of protein to stimulate
cell cycle
Oncogene can work without
growth factor due to point mutation
(issues signals by itself)
Cancer
2) p53 gene – mutated in 30% of
cancers
S-T-pathway that makes protein
that inhibits cell cycle
Uses many ways to prevent cell
from passing on mutations from
DNA damage
Damage to gene  no inhibition
cancer