Dyer Michael A, Qadeer Zulekha A, Valle-Garcia David, Bernstein Emily
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
Departments of Oncological Sciences and Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
Cold Spring Harb Perspect Med. 2017 Mar 1;7(3):a026567. doi: 10.1101/cshperspect.a026567.
Recent genome sequencing efforts in a variety of cancers have revealed mutations and/or structural alterations in and , which together encode a complex that deposits histone variant H3.3 into repetitive heterochromatin. These regions include retrotransposons, pericentric heterochromatin, and telomeres, the latter of which show deregulation in /-mutant tumors. Interestingly, and mutations are often found in pediatric tumors, suggesting a particular developmental context in which these mutations drive disease. Here we review the functions of ATRX and DAXX in chromatin regulation as well as their potential contributions to tumorigenesis. We place emphasis on the chromatin remodeler ATRX, which is mutated in the developmental disorder for which it is named, α-thalassemia, mental retardation, X-linked syndrome, and at high frequency in a number of adult and pediatric tumors.
近期对多种癌症进行的基因组测序工作揭示了ATRX和DAXX基因中的突变和/或结构改变，它们共同编码一种复合物，该复合物将组蛋白变体H3.3沉积到重复性异染色质中。这些区域包括逆转录转座子、着丝粒周围异染色质和端粒，在ATRX/DAXX突变的肿瘤中端粒表现出调控异常。有趣的是，ATRX和DAXX突变常见于儿童肿瘤中，这表明在特定的发育背景下这些突变会引发疾病。在此，我们综述了ATRX和DAXX在染色质调控中的功能及其对肿瘤发生的潜在作用。我们重点关注染色质重塑因子ATRX，它在以其命名的发育障碍——α地中海贫血、智力发育迟缓、X连锁综合征中发生突变，并且在许多成人和儿童肿瘤中高频突变。
