title: ATRX and DAXX: Mechanisms and Mutations.
abstract: Recent genome sequencing efforts in a variety of cancers have revealed mutations and/or structural alterations inATRXandDAXX, 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 inATRX/DAXX-mutant tumors. Interestingly,ATRXandDAXXmutations 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.
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dyer
authors.affiliation: Departments of Oncological Sciences and Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York 10029.|Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
authors.forename: Zulekha A
authors.initials: ZA
authors.lastname: Qadeer
authors.affiliation: Departments of Oncological Sciences and Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
authors.forename: David
authors.initials: D
authors.lastname: Valle-Garcia
authors.affiliation: Departments of Oncological Sciences and Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York 10029.|Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
authors.forename: Emily
authors.initials: E
authors.lastname: Bernstein
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000818:Animals; D002648:Child; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D056970:Co-Repressor Proteins; D004195:Disease Models, Animal; D006657:Histones / Q000378:metabolism; D006801:Humans; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D051379:Mice; D018832:Molecular Chaperones; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D016615:Telomere; D000075924:X-linked Nuclear Protein / Q000235:genetics*; D017085:alpha-Thalassemia / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D006657:Histones; D018832:Molecular Chaperones; D009687:Nuclear Proteins; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein