MBB 125 PB Lec 24 Epigenetics And Cance Hellip 
MBB 125
Molecular Physiology of Eukaryotic Systems
Lecture 24
Epigenetics and
Cancer: Disease of the Genome
National Institute of Molecular Biology & Biotechnology
University of the Philippines Diliman
EPIGENETICS
Epigenome and Chromatin Organization
E
Study of heritable changes in gene activity that are not attributable to alterations in genetic sequence
Potential point of crosstalk between the genome and the env’t ex: identical twins http://www.resverlogix.com/blog/wp-content/uploads/2013/02/epigenetics_large-1024x804.jpg Drivers of Epigenetic Mechanisms
*Co-regulators: dictate transcription of gene
http://www.nature.com/nrd/journal/v12/n12/images/nrd4154-f1.jpg
Drivers of Epigenetic Mechanisms
http://www.nature.com/ni/journal/v11/n7/images/ni0710-565-F1.jpg
Drivers of Epigenetic Mechanisms
Nucleosomes can slide relative to each other
Nat Biotechnol. 2010 Oct;28(10):1057-68
DNA Methylation
Occurs in the context of CpG dinucleotides that are clustered in regions called CpG islands
CpG islands - more than 200 bases w/ G+C content of at least 50% and a ratio of observed to statistically expected CpG frequencies of at least
0.6%
CpG island shores - region of lower CpG density that lie in close proximity (~2kb) of CpG island
DNA methylation is most commonly associated with silenced genomic regions- transposable elements, repetitive sequences, imprinted genes and inactive X chromosome
Mechanism of DNA methylation-dependent gene silencing:
1. Recruitment of methyl-CpG binding proteins (MBD) which then recruit histone or chromatin remodeling complexes
2. Inhibits the binding of transcription factors to their target sites
*jumping genes - can copy paste or jump out
Nat Biotechnol. 2010 Oct;28(10):1057-68
DNA Methylation
Methylation at CpG island shores is also closely associated w/ transcriptional inactivation 70% of differentially methylated regions in reprogramming are associated w/
CpG island shores
Ubiquitously expressed genes are commonly
Molecular Physiology of Eukaryotic Systems
Lecture 24
Epigenetics and
Cancer: Disease of the Genome
National Institute of Molecular Biology & Biotechnology
University of the Philippines Diliman
EPIGENETICS
Epigenome and Chromatin Organization
E
Study of heritable changes in gene activity that are not attributable to alterations in genetic sequence
Potential point of crosstalk between the genome and the env’t ex: identical twins http://www.resverlogix.com/blog/wp-content/uploads/2013/02/epigenetics_large-1024x804.jpg Drivers of Epigenetic Mechanisms
*Co-regulators: dictate transcription of gene
http://www.nature.com/nrd/journal/v12/n12/images/nrd4154-f1.jpg
Drivers of Epigenetic Mechanisms
http://www.nature.com/ni/journal/v11/n7/images/ni0710-565-F1.jpg
Drivers of Epigenetic Mechanisms
Nucleosomes can slide relative to each other
Nat Biotechnol. 2010 Oct;28(10):1057-68
DNA Methylation
Occurs in the context of CpG dinucleotides that are clustered in regions called CpG islands
CpG islands - more than 200 bases w/ G+C content of at least 50% and a ratio of observed to statistically expected CpG frequencies of at least
0.6%
CpG island shores - region of lower CpG density that lie in close proximity (~2kb) of CpG island
DNA methylation is most commonly associated with silenced genomic regions- transposable elements, repetitive sequences, imprinted genes and inactive X chromosome
Mechanism of DNA methylation-dependent gene silencing:
1. Recruitment of methyl-CpG binding proteins (MBD) which then recruit histone or chromatin remodeling complexes
2. Inhibits the binding of transcription factors to their target sites
*jumping genes - can copy paste or jump out
Nat Biotechnol. 2010 Oct;28(10):1057-68
DNA Methylation
Methylation at CpG island shores is also closely associated w/ transcriptional inactivation 70% of differentially methylated regions in reprogramming are associated w/
CpG island shores
Ubiquitously expressed genes are commonly