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Published by: 3d3 on Oct 25, 2010
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Exploring Your Genome
Week 9 : EpigenomicsLecture 1: Introduction
Thegenomeis a sequence of nucleotides that istransmitted to the next generation
Theepigenomeis the unique collection of modifications tothe nucleotides and associated proteins
These modifications control access to the genome itself 
The epigenome is another level of genetic information
“Epi” is Greek for on, above, near 
The epigenome is the answer to manybig questions
How does one genome result in so manydifferent cells and developmental stages?
How can two people with the same exactgenome (twins) develop radically differentfunctional outcomes (phenotypes)?
How can environmental exposure inparents lead to heritable, but non-nucleotide, changes in future generations?
Epigenomics: The Next Frontier 
Building on the Human Genome Project
Epigenome refers to the genome-widedistribution of all modifications tochromatinin a cell
Epigeneticsis the study of heritablechanges in gene function that are not due toa change in DNA sequence
(differentphenotypes, same genotype)
First, let’s review Chromatin
Chromatin is the complex of DNA and itsassociated proteinsThe proteins are mostlyhistones
Chromatin in Eukaryotic cells
DNA is packed by wrapping around histone proteins
Packed DNA and histones formnucleosomes
Histone proteins have short “tails”DNA in the densely packed state is not usually transcribedbecause the transcriptional machinery cannot access theDNADNA packing is a method of gene expression control: packedDNA = unreadable genes; open DNA = readable genesEpigenetic marksare modifications that are made to the DNAor to the histonesThe modifications can be proteins or chemical groups. Theyattach to the nucleotides directly or to the histone tails
Epigenetic marks
The marks, or modifications, occur normallythroughout a lifetime
The marks help to control access to thegenes - turning genes on/off throughdifferent stages of development anddifferentiation
of epigenetic mechanisms
1.Methylation of Cytosines2.Histone tail modification3.Chromatin binding proteins4.Non-coding RNAs
There are other types, but these are the main ones.Discovering new mechanisms of epigenetic control is aHOT area of research.
1. Methylation
The best known and best studied type of epigeneticmodification
Methylation of DNA has been studied for years
DNA and histones can both be methylated
Used as method to regulate gene expression
Typically, methylation of DNA blocks transcription andrepresses expression
Cytosines in CG rich regions are the targets of methylation (CGCGGGCCGCCGC)
CG rich regions are near mammalian genes
Methyl group is added to cytosines
Methylated cytosineprevents gene expressionbyblocking access of transcriptional machinery or bycondensing the DNA
2. Histone Modification
Histone tails are targets of modification.Chemical groups attach to the tails and helpto repress or activate transcription of DNA
Until recently, these twomechanisms of epigeneticswere the only onesstudied. There has beena boom in epigeneticresearch in the past fewyears.
3. Chromatin binding proteins
There are proteins thatbind to the epigeneticmarks like methylatedbases and help to repressor activate transcription.
4. Non-coding RNA
Non-coding RNAs are small RNAsequences that do NOT code forproteins. They were recently discoveredin the HG. Remember, that much of theHG is transcribed into RNA but nottranslated. Perhaps the “Junk” DNA ispart of the epigenetic mechanism. Non-coding RNAs have been identified ashelping to keep DNA in a tightly woundstructure.Non-coding RNAs playa role in X-inactivation. Here, theXist RNA coats the Xchromosome to keep itinactive.
Normal Epigenetic Roles
Cell differentiation
Gene regulation in response toenvironmental factors

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