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Department
Biology
Course Code
BIO207H5
Professor
Nicole Myers

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Kamalpreet Singh ©
Encode Explained
Basically Results of Various Studies of Genome.
Encyclopedia of DNA elements (ENCODE)
o Goal = Describe the list of Functional elements that compose the human genome.
Combining these elements in the right amounts = information needed to make up
all types of cells, body organs and basically an entire person.
o Initially focused on just 1% of the genome and results hinted that list of human genes
was incomplete.
doubts whether the results should be extended to the whole genome.
o Today Encode is based upon 1,640 genome wide data sets from 147 cell types.
Interesting Finding
o 80% of the genome = elements linked to the biochemical functions
Disproves "Human genome is mostly JUNK DNA"
Space between genes is filled with
Enhancers (regulatory DNA elements)
Promoters (sites at which DNA's transcription into RNA is started)
Many initially ignored areas that encode RNA transcripts that are not
translated into proteins ; Regulatory roles perhaps.
Results also showed that DNA variations linked with certain diseases lie inside
or very close to non-coding functional DNA elements.
New ways to link genetic variation and disease.
Ultra-deep sequencing of RNAs from many different cell lines and from certain compartments
within the cells lead to the conclusion:
o 75% genome = transcribed at some point in cells
o Genes are highly interconnected with overlapping transcripts that are made from both
DNA strands.
Force us to redefine a gene and the minimum unit of heredity.
Chromatin related studies
o Based on DNase I hypersensitivity
Detects genomic regions where enzyme access and cleavage is not hindered by
chromatin proteins.
o Researchers found cell specific patterns of DNase I hypersensitive sites that shows
agreement with experimentally found and theoretically predicted binding sites of
transcription factors.
o Also doubled the # of known recognition sequences for DNA-Binding proteins in human
genome.
o Found a 50 BP sequence that is found in many promoters.
Gerstein + friends = Theory behind the links of transcription factor networks.
o study attempts to clarify hierarchies of the transcription factor networks and assign
simple functions to genome elements.
Kamalpreet Singh ©
ENCODE also aims to map more than 1,000 long range signals that help communication
between the various elements of DNA in each cell type.
o Findings disprove the fact that regulation of a gene is dominated by its closeness to the
nearest regulatory elements.
Future Challenges for ENCODE
o Looking at the Dynamic aspects of gene regulation.
Right now we only really consider one event at a time. The combined effect may
be different from what we think.
o Figure out how the individual genomic components combine to create gene networks
and biochemical pathways that do complex functions (Cell-cell communication) that let
organs and tissues to develop.
o Use the Vast data (still increasing) from genome-sequencing projects to understand a
range of human phenotypes (traits) from normal developmental processes such as
ageing to diseases such as Alzheimer's.
To Solve Future challenges = Invest LOTS of time in studying simple organisms.
Figure 1
Kamalpreet Singh ©
Figure One
The Encode project gives us much more information about the human genome than can be found
inside the DNA sequence.
o It tells us about
Functional genomic elements
Control the development and function of a human.
The degree of DNA methylation and chemical modifications to histones
Influence the rate of transcription of DNA and RNA molecules.
Histones = Proteins around which DNA is wrapped to make Chromatin
Long-range chromatin interactions ( such as looping)
Change the relative proximities of different chromosomal areas in 3D
and also affect transcription.
Binding activity of transcription-factor proteins and the architecture (location &
sequence) of gene-regulatory DNA elements.
Gene-regulatory DNA elements
o Promoter regions upstream of the point where transcription of
an RNA molecule starts
o Distant (long-range) regulatory elements
Accessibility of the genome to the DNA-cleavage protein (DNase I)
Accessible areas = DNase I hypersensitive sites
o We think Indicate certain sequences where the binding of
transcription factors and transcription machinery proteins has
caused nucleosome displacement.
o Also records
the sequences of and quantifies RNA transcripts from Non-coding and protein-
coding areas.
Expression Control
To understand gene expression regulation one has to understand chromatin organization
o ENCODE spent a lot time trying to understand chromatin organization.
Also talked about the key role of transcription factors in shaping the chromatin
landscape.
Some of the analyses = Confirmation of other smaller research.
Gave fresh insight into regulatory pathways and found an abnormal number of
regulatory elements.
Especially for the DNase I hypersensitive sites (DHSs) & DNA binding
of transcription factors.
o DHSs = genomic regions that are assessable to DNA cutting
enzymes (DNase I ) due to the displacement of nucleosomes by
DNA-binding proteins.

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Description
Kamalpreet Singh Encode Explained Basically Results of Various Studies of GenomeEncyclopedia of DNA elements ENCODEo GoalDescribe the list of Functional elements that compose the human genome Combining these elements in the right amountsinformation needed to make up all types of cells body organs and basically an entire person o Initially focused on just 1 of the genome and results hinted that list of human genes was incompletedoubts whether the results should be extended to the whole genomeo Today Encode is based upon 1640 genome wide data sets from 147 cell types Interesting Findingo 80 of the genomeelements linked to the biochemical functions Disproves Human genome is mostly JUNK DNA Space between genes is filled with Enhancers regulatory DNA elementsPromoters sites at which DNAs transcription into RNA is startedMany initially ignored areas that encode RNA transcripts that are not translated into proteinsRegulatory roles perhaps Results also showed that DNA variations linked with certain diseases lie inside or very close to noncoding functional DNA elements New ways to link genetic variation and disease Ultradeep sequencing of RNAs from many different cell lines and from certain compartments within the cells lead to the conclusion o 75 genometranscribed at some point in cells o Genes are highly interconnected with overlapping transcripts that are made from both DNA strandsForce us to redefine a gene and the minimum unit of heredity Chromatin related studieso Based on DNase I hypersensitivityDetects genomic regions where enzyme access and cleavage is not hindered by chromatin proteins o Researchers found cell specific patterns of DNase I hypersensitive sites that shows agreement with experimentally found and theoretically predicted binding sites of transcription factorso Also doubled theof known recognition sequences for DNABinding proteins in human genome o Found a 50 BP sequence that is found in many promoters GersteinfriendsTheory behind the links of transcription factor networks o study attempts to clarify hierarchies of the transcription factor networks and assign simple functions to genome elementsKamalpreet SinghENCODE also aims to map more than 1000 long range signals that help communication between the various elements of DNA in each cell typeo Findings disprove the fact that regulation of a gene is dominated by its closeness to the nearest regulatory elements Future Challenges for ENCODEo Looking at the Dynamic aspects of gene regulationRight now we only really consider one event at a time The combined effect may be different from what we think o Figure out how the individual genomic componentscombine to create gene networks and biochemical pathways that do complex functions Cellcell communication that let organs and tissues to develop o Use the Vast data stillincreasingfrom genomesequencing projects to understand a range of human phenotypes traitsfrom normal developmental processes such as ageing to diseases such asAlzheimersTo Solve Future challengesInvest LOTS of time in studying simple organismsFigure 1
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