EPIGENOMICS - EPIGENETICSAfiono Agung Prasetyo Satellite DNASatellite DNA comprises very long arrays of tandem repeats typically 100 kb to several megabases in size, the repeat unit length varying between 5 and 11 bp!Minisatellite DNA arrays are of intermediate size and typically span between 100 bp and "0 kb, with each repeat unit between # and 100 bp in length!Microsatellite DNA comprises short arrays less than 100 bp in size, made up of simple tandem repeats 1$# bp in length! forensic EPIGENOME%he eukaryotic genome is packaged into nucleosomes, which form the basal unit of chromatin, the physiological form of &'A within the nucleus! Apart from its function in compacting the immense nuclear &'A molecules, chromatin also serves as a platform onto which multiple signalling pathways converge to cooperate in determining the e(pression status of m)'As and other *non+coding, )'A molecules! -pigenetic profile analysis aims to determine what changes on the nucleosomes cooperate to establish and maintain &'A se.uence+independent heritable traits such as those determining cell identity! CpG-island)oughly half of the human promoters are located within a /p0+island, a region in which the /p0 dinucleotide motif is overrepresented relative to the average genome cytosine methylation, occurring at position 5 of the cytosine pyrimidine ring in /p0 dinucleotides -pigenetic processes are essential for normal cellular development and differentiation, and allow the regulation of gene function through non+mutagenic mechanisms! %he methylation of the /p0 sites, over+represented in /p0+islands in the promoter regulatory regions of many genes, disrupts the binding of transcription factors and attracts methyl+binding proteins that initiate chromatin compaction and gene silencing! 1istone modification, another epigenetic mechanism mediating gene e(pression, affects chromatin organization via the processes of histone acetylation, histone methylation, and histone phosphorylation! 2ethyl+&'A binding proteins are mostly part of multi+protein comple(es that contain chromatin modifyingactivity represented by histone+deacetylases *1&A/s, and chromatin remodelers Primary Defects in DNA Methylation and Their Diseases abnormal &'A+methylation is found in many genes in cancer and other conditions %he proteins that are known to methylate &'A are &'2%1, &'2%3A and &'2%34! 5ive proteins interact with methylated / *me+/, namely 24&1, 24&", 24&3, 24&6 and 2e/P"! %hese processes are fundamental for the function of the cell, and it is surprising that mutations in these proteins show manifestations in only selected cell types! 2utations in both alleles of the gene &'2%34 lead to a recognizable syndrome of severe, often lethal immunodeficiency, centromeric instability and facial anomalies *7/5, syndrome i!e! it is inherited as an autosomal recessive trait! /ytogenetic analysis show severe disturbances of the pericentromeric regions of chromosomes 1, 8 and 1#, known to contain satellite &'A! 2ost patients with this phenotype have been shown to harbour mutations in the &'A methyltransferase se.uence motifs of &'2%34 and a recognisable lack of de novo methylation of the pericentric heterochromatic repeats! Defects in Histones Histone Modifyin! En"ymes and General Transcription #actors and Their Diseases2utations in these proteins most often result in malignant transformation including both solid tumors and leukemia! Another common result is a syndrome, i!e! a mi(ture of clinical symptoms from different cells and tissues, which is logical since basic machineries are perturbed! 2utations in genes encoding two histones have been significantly associated with cancer9 17:%1114 with colorectal cancer and 17:%1167 with non+1odgkin;s 133 genes encoding %5s are known to cause syndromes, autosomal dominant, autosomal recessive and =+linked recessive diseases, that each are relatively rare! 2utated transcription factors in common diseases90A%A binding protein " *0A%A",9 early onset coronary artery disease1epatocyte nuclear factor 6 alpha *1'56A,9 maturity+onset diabetes of the young *2>&?, type 17nsulin promoter factor 1 *7P51,9 pancreatic agenesis, 2>&? 6, type " diabetes7nterferon regulatory factor 5 *7)55,9: