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• W1523220187 abstract "Chromatin is a highly ordered structure consisting of repeats of nucleosomes connected by linker DNA. It consists of DNA, histone, and nonhistone proteins condensed into nucleoprotein complexes and it functions as the physiological template of all eukaryotic genetic information. Histones are small basic proteins containing a globular domain and a flexible charged NH2 terminus known as the histone tail, which protrudes from the nucleosome. Epigenetic codes are set up by modifications on the DNA (methylation) or on the histones (acetylation, methylation, phosphorylation, ubiquitination, and ADP ribosylation, etc.), by different classes of enzymes in a precise and targeted manner. Posttranslational modification to histones affects chromatin structure and function resulting in altered gene expression and changes in cell behavior. These modifications do not alter the primary sequence of DNA but have an impact on gene expression regulation, most frequently gene suppression. They lead to pathological states in hematopoietic system resulting in acute leukemia. DNA methylation is catalyzed by DNA methyltransferases (DNMTs), of which three active enzymes have been identified in mammals, namely DNMT1, DNMT3A and DNMT3B. DNMT1 is responsible for maintaining pre-existing methylation patterns during DNA replication, while DNMT3A and DNMT3B are required for initiation of de novo methylation. Acetylation is a reversible process. The balance between acetylation (transcriptional activation) and deacetylation (transcriptional repression) is regulated by histone acetyltransferase (HATs) and histone deacetylases (HDACs) in specific lysine residues in the N-termini of histone tails and/or in transcription factors (eg, p53, E2F1, GATA1, RelA, YY1, and Mad/Max) without directly binding to the DNA (Minucci et al., 2006, Gallinare et al., 2007), and is critical in regulating gene expression. Mammalian HDACs are classified into three classes based on their homology to yeast HDACs. Class I HDACs (HDAC1, 2, 3, 8, and 11) are homologues of Sacharomyces cerevisiae histone deacetylase Rpd 3 (reduced potassium dependency 3) and those with greater similarity to yeast Hda1, are class II HDACs (Gray & Ekstrom, 2001; Gao et al., 2002; Kao et al., 2002). Class III HDACs are called Sirtuins, which are homologoues of yeast sir2 (silence information regulator). Histones can be mono-, di-, or tri-methylated at lysine and arginine residues by HMTs, and the recent identification of histone lysine demethylases such as KDM1/LSD1 and the Jumonji-domain (JMJD)-containing protein family shows that histone" @default.
• W1523220187 created "2016-06-24" @default.
• W1523220187 creator A5030540224 @default.
• W1523220187 creator A5059062585 @default.
• W1523220187 creator A5059450725 @default.
• W1523220187 creator A5071975204 @default.
• W1523220187 creator A5077729211 @default.
• W1523220187 creator A5083253456 @default.
• W1523220187 date "2011-12-22" @default.
• W1523220187 modified "2023-09-23" @default.
• W1523220187 title "Epigenetics and Targeted Therapy in Acute Leukemia" @default.
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