Download Structure of promoter

Promoters
Oriane Broustal
BIO 535
Promoters
• About promoters ( structure, function,…)
• Two types of human promoters based on CG
content
• Bidirectional promoters in human genome
Questions:
• What are the differences between eukaryotic and
prokaryotic promoters?
• Explain what you know about bidirectional promoters
in human genome.
Function of promoter
•
ARN polymerase binding site
•
Initiation of transcription
•
control by regulatory sequences
=> control the expression of genes
Prokaryotic promoters
• - 35 box and – 10 box ( also called Pribnow box) are consensus
sequences
• The two boxes are far appart from a specific distance, so they are located
on the same face of the double helix.
Prokaryotic promoters
•
Possible to have variations in the
consensus sequences
•
There is often a correlation
between level of expression of a
gene and degree to which the –35
and –10 region agree with their
consensus sequence
Eukaryotic promoters
•
•
•
•
There are two parts:
- The core promoter or basal promoter
- Upstream promoter element ( one or more)
Core promoter is constituted by the TATA box and the transcriptional start site
(TSS)
Initation complexe bind to the core promoter
Upstream elements are responsable of the regulation of the transcription
Eukaryotic promoters
Regulation of transcription
•
Two categories of regulatory sequences:
- Activating sequences= Enhancers
- Repressing sequences = Silencers
•
In Prokaryotes, regulatory sequences are located around the promoter
•
In Eukaryotes, regulatory sequences are often upstream the promoter at
about 100 bp away, but sometime they are far away (several thousand
nucleotides) or they can also be dowstream from the promoter
Two types of promoter based on CpG
content in human genome
•
CpG = Cytosine followed by a Guanine ( linked together by a phosphate)
•
CpG island = regions of the DNA which have a high concentration of CpG
•
Based on CpG content, there are two types of promoters:
- with high CpG content ( called HCG) = 72%
- CpG content characteristic of averall genome = 28%
•
In HCG, the CpG region is symetric and peaks aroud the core promoter
(specially around the TSS).
DNA methylation
• Occurs on Cytosine in 5’ position
• inhibits transcription if methylated region is
close to a promoter, which is the case for CpG
islands.
• CpG island associated with HCG are often
hypomthylated =>more expressed . It is often
associted with House-keeping gene.
•Whereas, in promoter with lower CpG, CpG
are often methylated => inhibit the expression.
This often finds in tissue-specific genes.
• With CpG islands around promoter, posibility
to have methylation mediated regulation
DNA methylation
Cytosine methylation and mutation
Bidirectional promoters in human
genome
•
Pairs of genes control by same promoter but located on opposite strand and
opposite direction. Their TSS are separated by less than 1,000 bp.
•
In general, they are rich in CpG content
•
Function of genes represented in bidirectinal class are often: DNA repair
genes, chaperone protein, and mitochondrial genes.
•
Seem to be conserved in evolution
Bidirectional promoters in human
genome
•
Genes control by bidirectional promoters are oftne coexpress, but a minority of
bidirectional genes have a mutual exclusive expression.
•
No correlation between lenght of promoter and degree of expression
•
Cell type seems to affect the activity of the promoter. Indeed, scientist made an
experiment with different cell lines.
Bidirectional promoters in human
genome
•
Genes of bidirectional promoters
shared some element of the
promoter
•
If there is deletion of TSS of one
transcript, the transcription of the
gene on the opposite direction is
increased.
•
Conclusion: bidirectional promoter
acts as an inseparable functional
units which reglate the
transcription of both genes.
Promoters ( conclusion)
• About promoters ( structure, function,…)
• Two types of human promoters based on CG
content
• Bidirectional promoters in human genome
References:
Robert J. Brooker. Genetics, Analysis & Principle (second edition)
T.A. Brown. Genomes (second edition)
Wikipedia web site
Serge Saxonov, Paul Berg, and Douglas L. Brutlag. A genome-wide analysis of
CpG dinucleotides in the human genome distinguishes two classes of promoters.
PNAS (January, 23, 2006)
Nathan D. Trinklein, Shelley Force Aldred, Sara J. Hartman, Diane I. Schroeder,
Robert P. Otillar and Richard M.Myers. An Abundance of Bidirectional Promoters
in the Human Genome. Genome Research (2004)