Genomic level

Prokary Eukaryotic
otic
Heterochromatin Highly compacted DNA where DNA winds more tightly
around histones Limits access of RNA polymerase and transcription factors
to promoters of genes
Euchromatin less compacted DNA where DNA winds less tightly around
histones Promotes access of RNA polymerase and transcription factors to
promoters of genes
1. Chromatin remodeling complexes
-

Alter structure of nucleosomes

DNA less tightly bound to histones
allows RNA polymerase and transcription factors to promoters of
genes to initiate transcription

DNA more tightly coiled around histones

prevent RNA polymerase and transcription factors to promoters of
genes thereby
blocking transcription

2. DNA Methylation* permanent :

-

addition of methyl group to selected cytosine nucleotide located in

sequence CG

Prevents transcription by
Blocking binding of transcription factors prevent assembly of
transcription initiation complex at promoter

Recruiting DNA-binding proteins (repressive chromatin

remodeling complex, transcriptional repressors, histone

deacetylase) to condense chromatin gene silencing/ no gene
expression
3. Histone acetylation/ deacetylation
-

Allows chromatin to decondense and condense

Histone acetylase: Acetylation of histones addition of acetyl

groups (-COCH3) removes +ve charge on histones
decrease electrostatic interactions binding between DNA
and histones loosen more accessible allow transcription

Histone deacetylase: deacetylation of histones removal of

acetyl groups tighter interactions between DNA and
histones inhibiting transcription

4. Gene amplification
- Normal number of all other genes except for gene of interest which
exists in high copy number during transcription and translation,
increased copies of mRNA, increased copies of required protein
obtained

X chromosomal inactivation: if 2x chromosomes expressed females =

double gene products 1 x chromosome is inactivated (extensive
formation of heterochromatin, histone modification, DNA Methylation)
- Highly compacted chromosome Barr body formed most
genes cannot be transcribed prevent excessive amount of
gene products accumulating

Transcriptional level +post transcription

Prokaryotic
Eukaryotic
1. mRNA stability/half
a. PROXIMAL CONTROL ELEMENTS
- Non coding DNA that lies directly
life
upstream of the transcription start site
- short mRNA half
bound by general transcription factor
lives allow
PROMOTERS
rapid degradation
Recognition site for binding of
- binding of
transcription factors and RNA polymerase
antisense RNA
*critical elementsrecruit RNA
complementary to
polymerase and general transcription
mRNA reduce
factors
half life, block
translation
2. Binding of small
ribosomal subunit
-

Binding of
translational

*Critical elements not that crucial

in controlling gene expression
presence of enhancer/ silencers in
Eukaryotic cells
o

TATA box at -25 site determine

precise location of transcription

repressor protein
near the shineDalgarno*
sequence
Binding of antisense RNA
complementary to
mRNA near shineDalgarno
sequence
prevent binding
of small ribosomal
subunit
ribosomes
cannot assemble

* (5-AGGAGG-3) found
a few nucleotides
upstream of each AUG
start codon. Small
ribosomal subunit bind
to this sequence so
that the start codon
can be correctly
positioned in the
subunit before initiator
tRNA and large
ribosomal subunit
come along for
translation
3. Initiation factor
-

Availability of
initiation
factors* controls
initiation of
translation

* Initiation factors
required for proper
positioning of small
ribosomal subunit
together with initiator
tRNA on the mRNA and
the subsequent
recruitment of the
large ribosomal
subunit

start site
CAAT box at -75 site, GC box at -90
site (multiple copies) recruit
general transcription factors and
RNA polymerase

b. DISTAL CONTROL ELEMENTS

- Non-coding DNA that can be located
thousands of nucleotides upstream or
downstream of the gene, even within an
intron bind to other factors specific
transcription factors
ENHANCERS
Bound to activators increase efficiency
of transcription/increase rate of
transcription Gene activation
Positive regulatory elements involved in
upregulation promote assembly of
transcription initiation complex via
interaction with activators*
*Activators bind to enhancer to
increase efficiency by
o Promoting assembly of
transcription initiation complex
Binding of activators to
enhancers bending of spacer
DNA (regions of non-transcribed
DNA between genes) direct
interaction of activators with RNA
polymerase promote
assembly of transcription
intiation complex
Increasing accessibility to promoter
DNA
bound activators recruit histone
acetylase and chromatin
remodeling complex to
decondense chromatin greater
accessibility of general
transcription factors and RNA
polymerase to promoter
SILENCERS
Bound to repressors decrease
o

efficiency of transcription gene

repression
Negative regulatory elements
downregulation prevent assembly of
transcription initiation complex
1. Interfering with action of activator
o Competitive DNA binding
prevent activator binding
o Masking activation surface
prevent interaction with general
transcription factor
o Direct interaction with general
transcription factor inhibit
assembly
2. changing chromatin structure
Post-transcriptional
Pre mRNA modification mature mRNA
Alters mRNA stability: affects amt of proteins made
1. Capping at 5 end of mRNA
- Addition of 7-methylguanosine cap to 5
end of mRNA
- Processing (mRNA splicing and
polyadenylation
- Export out of nucleus
- Half life
- Translation (subsequent binding of
initiation factors helps recruitment of
mRNA to small ribosomal subunit)
2. Splicing of pre-mRNA: Introns excised, exons
joined by spliceosome
Alt splicing 1 gene diff mRNAdiff
polypeptides
3. Adding a poly-A tail to 3end of mRNA:
adenosine monophosphate
(ribonucleotide)added by poly-A
polymerase
- Enhances half life degradation by
ribonucleases in nucleus and cytoplasm
- Serves as a signal to direct export of
mature mRNA from nucleus to cytoplasm
- Works together w 5 Cap to regulate
mRNA translational efficiency

translatio Postnal translatio

Translational level + post translational

Prokaryotes
Eukaryotes
1. mRNA stability
1. mRNA stability
- short mRNA half lives:
- stability influenced by length
rapid degradation
of poly-A-tail (degraded by
- binding of antisense RNA
ribonuclease in 3 to 5
complementary to mRNA:
1. Covalent
modification to form
direction)
- Covalent modification
functional proteins from
- Phosphorylation/
inactive form!!
dephosphorylation
- Further processing
- Protein degradation
(glycosylation, disulfide bond