TY - CHAP M1 - Book, Section TI - Epigenetics A1 - Cairns, Bradley R. A2 - Kaushansky, Kenneth A2 - Lichtman, Marshall A. A2 - Prchal, Josef T. A2 - Levi, Marcel M. A2 - Press, Oliver W. A2 - Burns, Linda J. A2 - Caligiuri, Michael Y1 - 2015 N1 - T2 - Williams Hematology, 9e AB - SUMMARYEpigenetics involves a heritable change in phenotype without a change in genotype–with the inheritance of particular chromatin and transcription states often underlying the mechanism. Chromatin regulates gene expression by controlling the density and positioning of nucleosomes, and by the use of histone- and DNA-modifying enzymes. Chromatin and transcription factors drive proper differentiation decisions through their coregulation of key factors in development and proliferation. Of particular interest to hematologists are instances when misregulation/mutation of chromatin factors drives hematologic malignancies and myeloproliferative disorders. Here, fusion proteins that involve the mistargeting of chromatin regulators have been known for decades. More recently, high-throughput sequencing and other genomics approaches have revealed mutations in many types of chromatin regulators in hematologic malignancies, including mutations in chromatin remodelers, DNA methylation regulators, histone modification enzymes, and metabolic enzymes affecting epigenetic cofactors. Overall, these studies reveal a consistent theme: epigenetic and genetic mutations confer both variation and plasticity to the transcriptome, and when combined with selection, arrive at transcriptomes that promote proliferation, survival, and adaptability. This chapter addresses these mechanistic principles of chromatin, and their misregulation in hematologic malignancies, as well as emerging therapeutic approaches. SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/03/28 UR - accessmedicine.mhmedical.com/content.aspx?aid=1121089335 ER -