Paluch Benjamin E, Naqash Abdul R, Brumberger Zachary, Nemeth Michael J, Griffiths Elizabeth A
Department of Pharmacology, Center for Pharmacology and Genetics Building (CGP), Roswell Park Cancer Institute (RPCI), Elm and Carlton Street, 14263 Buffalo, NY, USA.
Catholic Health, State University of New York at Buffalo (SUNY), 2157 Main Street, 14214 Buffalo, NY, USA.
Blood Rev. 2016 Jul;30(4):285-95. doi: 10.1016/j.blre.2016.02.002. Epub 2016 Feb 26.
With recent advances in cellular biology, we now appreciate that modifications to DNA and histones can have a profound impact on transcription and function, even in the absence of changes to DNA sequence. These modifications, now commonly referred to as "epigenetic" alterations, have changed how we understand cell behavior, reprogramming and differentiation and have provided significant insight into the mechanisms underlying carcinogenesis. Epigenetic alterations, to this point, are largely identified by changes in DNA methylation and hydroxymethylation as well as methylation, acetylation, and phosphorylation of histone tails. These modifications enable significant flexibility in gene expression, rather than just turning genes "ON" or "OFF." Herein we describe the epigenetic landscape in the regulation of gene expression with a particular focus on interrogating DNA methylation in myeloid malignancy.
随着细胞生物学的最新进展,我们现在认识到,即使在DNA序列没有变化的情况下,对DNA和组蛋白的修饰也会对转录和功能产生深远影响。这些修饰现在通常被称为“表观遗传”改变,它们改变了我们对细胞行为、重编程和分化的理解,并为癌症发生的潜在机制提供了重要见解。到目前为止,表观遗传改变主要通过DNA甲基化和羟甲基化的变化以及组蛋白尾部的甲基化、乙酰化和磷酸化来识别。这些修饰使基因表达具有显著的灵活性,而不仅仅是将基因“开启”或“关闭”。在此,我们描述基因表达调控中的表观遗传格局,特别关注对髓系恶性肿瘤中DNA甲基化的研究。