Transcript Vertebrate Gene Cis-Regulation - A computational tour of the human

MW 11:00-12:15 in Redwood G19
Profs: Serafim Batzoglou, Gill Bejerano
TA: Cory McLean
http://cs273a.stanford.edu [Bejerano Aut07/08]
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Lecture 11
Human Genes
Vertebrate Gene Cis-Regulation
http://cs273a.stanford.edu [Bejerano Aut07/08]
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What People Largely Expected to Find
DNA
proximal: in 103 letters
3kb
http://cs273a.stanford.edu [Bejerano Aut07/08]
gene (how to)
control region
(when & where)
genome.ucsc.edu
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How They Measured
all human-mouse alignments
human-mouse
ancestral repeats alignment
Difference:
5% of
Human Genome
[Mouse consortium, Nature 2002]
http://cs273a.stanford.edu [Bejerano Aut07/08]
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Other Ways to Measure
[Lunter et al, 2006]
[Cooper et al., 2005]
http://cs273a.stanford.edu [Bejerano Aut07/08]
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What They Found
Human
Genome:
3*109 letters
1.5%
known
function
compare to other species
>50%
junk
>5% human genome functional
3x more functional DNA than known!
~106 substrings do not code for protein
What do they do then?
[Science 2004 Breakthrough of the Year, 5th runner up]
http://cs273a.stanford.edu [Bejerano Aut07/08]
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The Gene-ome makes < 2% of the H.G.
[Human Molecular Genetics, 3rd Edition]
http://cs273a.stanford.edu [Bejerano Aut07/08]
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Gene Finding – The Practice
Challenge:
“The genes, the whole genes, and nothing but the genes”
Problems:
spliced ESTs  legitimate gene isoform?
predicting gene isoforms
tissue/condition specific genes / gene isoforms
single exon genes
pseudogenes
Practice:
http://cs273a.stanford.edu [Bejerano Aut07/08]
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Evolution of Gene Finding Tools
etc
http://cs273a.stanford.edu [Bejerano Aut07/08]
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The Human Gene Set
[HGC, 2001]
http://cs273a.stanford.edu [Bejerano Aut07/08]
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[Celera, 2001]
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wrong!
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Horizontal Gene Transfer
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Horizontal Gene Transfer in the H.G.
…
[HGC, 2001]
http://cs273a.stanford.edu [Bejerano Aut07/08]
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Or is it?
[Kurland et al., 2003]
http://cs273a.stanford.edu [Bejerano Aut07/08]
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HGT between fish & their parasites
http://cs273a.stanford.edu [Bejerano Aut07/08]
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Gene regulation = when/where to make protein
gene (how to)
control region
(when & where)
DNA
~103 letters
http://cs273a.stanford.edu [Bejerano Aut07/08]
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Vertebrate Transcription Regulation
http://cs273a.stanford.edu [Bejerano Aut07/08]
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Unicellular vs. Multicellular
unicellular
multicellular
http://cs273a.stanford.edu [Bejerano Aut07/08]
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Vertebrate Gene Regulation
distal: in 106 letters
gene (how to)
control region
(when & where)
DNA
proximal: in 103 letters
http://cs273a.stanford.edu [Bejerano Aut07/08]
DNA binding
proteins
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Pol II Transcription
Key components:
• Proteins
• DNA sequence
• DNA epigenetics
Protein components:
• General Transcription factors
• Activators
• Co-activators
http://cs273a.stanford.edu [Bejerano Aut07/08]
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Activators & Co-Activators
Protein - Protein
Protein - DNA
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