Epigenomics Epi Geromics Jong Bhak Epigenetic Chromatin Structure
Epigenomics Epi. Geromics Jong Bhak
Epigenetic Chromatin Structure • Most epigenetic research has converged on the study of covalent and noncovalent modifications of DNA and histone proteins as the mechanisms that directly influence chromatin structure. • https: //www. youtube. com/watch? v=M 4 bo. Kud 1 MRk
Chromatin structure Gene Expression • This is because the local chromatin environment of a given gene strongly influences its expression.
Definition: Epigenomics • is the study of the complete set of epigenetic modifications on the genetic material of a cell, known as the epigenome.
Reversible • Epigenetic modifications are reversible modifications on a cell’s DNA or histones that affect gene expression without altering the DNA sequence. • Modificaion affects Next generation • Cloning
Differentiation and Development & Tumorigenesis. • Epigenetic modifications play an important role in gene expression and regulation, and are involved in numerous cellular processes such as in differentiation and development and tumorigenesis.
Epi. Geromics. • Epigenetic modifications play an important role in gene expression and regulation, and are involved in numerous cellular processes such as in differentiation and development and senescence.
Epigenomics Mechanisms RNA Interference Gene Expression Histone Modifications DNA Methylation DNA methylation, histone modifications, chromatin accessibility & small RNA transcripts
DNA Methylation Hypomethylation Hypermethylation http: //www. cellscience. com/reviews 7/Taylor 1. jpg
DNA methyltransferase The DNA methyltransferase (DNA MTase) family of enzymes catalyze the transfer of a methyl group to DNA methylation serves a wide variety of biological functions. All the known DNA methyltransferases use S-adenosyl methionine (SAM) as the methyl donor.
DNA (cytosine-5)methyltransferase 1 is an enzyme that in humans is encoded by the DNMT 1 gene. Function DNA (cytosine-5 -)-methyltransferase 1 has a role in the establishment and regulation of tissue-specific patterns of methylated cytosine residues. Aberrant methylation patterns are associated with certain human tumors and developmental abnormalities.
crystal structure of type i restriction enzyme ecoki m protein (ec 2. 1. 1. 72) (m. ecoki)
S-Adenosyl methionine (SAM-e, SAM, SAdenosyl-L-methionine, Ado. Met, ademetionine) is a common cosubstrate involved in methyl group transfers. SAM was first discovered in Italy by G. L. Cantoni in 1952
Natural Roles of DNA Methylation in Mammalian System Ø Imprinting Ø X chromosome inactivation Ø Heterochromatin maintenance Ø Developmental controls Ø Tissue specific expression controls
Heterochromatin
DNA Methylation and Cancer Robertson, Nature Reviews Genetics, Vol 6, 597
DNA Methylation and Aging -- Imprinting Disorder: • Beckwith-Wiedemann syndrom (BWS) • Prader-Willi syndrome (PWS) • Transient neonatal diabetes mellitus (TNDM) -- Repeat-instability diseases • Fragile X syndrome (FRAXA) • Facioscapulohumeral muscular dystroph -- Defects of the methylation machinery • Systemic lupus erythemtosus (SLE) • Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome
Histone Modifications http: //porpax. bio. miami. edu/~cmallery/150/gene/c 7. 19. 4. histone. mod. jpg
Histone Modifications http: //www. nature. com/nsmb/journal/v 14/n 11/images/nsmb 1337 -F 1. gif
Li e. al. (2007) Cell 128, 707
Histone Modifications in Relation to Gene Transcription Li e. al. (2007) Cell 128, 707
Histone Modifications and Human Diseases Coffin-Lowry syndrome is a rare genetic disorder characterized by and abnormalities of the head and mental retardation facial and other areas. It is caused by mutations in the RSK 2 gene (histone phosphorylation) and is inherited as an X-linked dominant genetic trait. Males are usually more severely affected than females. Rubinstein-Taybi syndrome is characterized by short stature, moderate to severe intellectual disability, distinctive facial features, and broad thumbs and first toes. It is caused by mutations in CREB-binding protein (histone acetylation)
RNA Interference (RNAi) http: //www. nature. com/ncpneuro/journal/v 3/n 7/images/ncpneuro 0551 -f 1. jpg
si. RNA Mediated Heterochromatin Maintenance
Technologies for Studying Epigenomics DNA Methylation Microarray or deep sequencing Irizarry et. Al. (2008) Genome Research 18(5): 780
Biosulfite Treatment of Cytosine Treatment of DNA with bisulfite converts cytosine residues to uracil, but leaves 5 -methylcytosine residues unaffected.
Bisulfite Sequencing
Bisulfite Sequencing
Non-methylation-specific PCR based methods
Knowing Difference? Importance of References And Accepting Difference
Genomic T 7 billion persons Genomic Variability 6 billion Bases Genomic Diversity Jong Bhak, under Bio. License
Geno+ Enviro=> Pheno (GEP/T graph) Geno Pheno/Trait Each Trait or Disease Cancer Flu Car accident Enviro the atom of environment Jong Bhak. Under Bio. License: public domain. 36
(Making) Variation is the driving force of the universe Phene Variation Gene Variation Environe Variation Jong Bhak. Under Bio. License: public domain 37
Genome : Envirome : Phenome • Genome = gene types + their variome • Envirome= environe types + their variome • Phenome= phene types + their variome Jong Bhak. Under Bio. License: public domain 38
Prediction is what we do All the algorithms in the world is to predict something Phenome • genome Uncertainty Envirome Jong Bhak. Under Bio. License: public domain ? 39
Complicated • Gene. Complexes Enviro. Comple xes Jong Bhak. Under Bio. License: public domain Phene. Comple xes 40
Structure in Species Genomes Matrix 6 billion people billion Bases x 3(? ) million animal species
Genomic T: Finding Structure in “Population” Matrix 6 billion people 7 billion Bases x 6 billion people Billion Genome Project (Bi. G) http: //billiongenome. com
Geno-Enviro-Pheno Tri. Point Comparative Genomic Sweet Spot Class Population Stratification Polymorphism Functional aberation Genus/Family, …. . Isolation (repro) Speciation, Functionally similar Distant homologs Functionally distinct
Aging and Cancer in a population Phenotypes by variations
The ultimate phenotype • Alive or Dead
Epigenetic Control of Aging • Ursula Muñoz-Najar and John M. Sedivy
Dynamic DNA/chromosome
Methylation pattern DNA methylation age of human tissues and cell types Steve Horvath
Histone and Protein modification
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