Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam 1066CX, The Netherlands
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam 1066CX, The Netherlands.
Genes Dev. 2021 Nov 1;35(21-22):1403-1430. doi: 10.1101/gad.348897.121.
Chromatin is highly dynamic, undergoing continuous global changes in its structure and type of histone and DNA modifications governed by processes such as transcription, repair, replication, and recombination. Members of the chromodomain helicase DNA-binding (CHD) family of enzymes are ATP-dependent chromatin remodelers that are intimately involved in the regulation of chromatin dynamics, altering nucleosomal structure and DNA accessibility. Genetic studies in yeast, fruit flies, zebrafish, and mice underscore essential roles of CHD enzymes in regulating cellular fate and identity, as well as proper embryonic development. With the advent of next-generation sequencing, evidence is emerging that these enzymes are subjected to frequent DNA copy number alterations or mutations and show aberrant expression in malignancies and other human diseases. As such, they might prove to be valuable biomarkers or targets for therapeutic intervention.
染色质具有高度动态性,其结构和组蛋白类型以及 DNA 修饰不断发生全局变化,这些变化受转录、修复、复制和重组等过程的调控。染色质解旋酶 DNA 结合(CHD)酶家族的成员是 ATP 依赖性染色质重塑酶,它们密切参与染色质动力学的调节,改变核小体结构和 DNA 可及性。酵母、果蝇、斑马鱼和小鼠的遗传研究强调了 CHD 酶在调节细胞命运和身份以及胚胎正常发育中的重要作用。随着新一代测序技术的出现,有证据表明这些酶经常发生 DNA 拷贝数改变或突变,并在恶性肿瘤和其他人类疾病中表现出异常表达。因此,它们可能被证明是有价值的生物标志物或治疗干预的靶点。