title: Reading between the Lines: "ADD"-ing Histone and DNA Methylation Marks toward a New Epigenetic "Sum".
abstract: Covalent modifications of both DNA and histones act in concert to define the landscape of our epigenome. In this review, we explore the interconnections between histone and DNA modifications by focusing on a conserved chromatin-binding regulatory domain, the ATRX-DNMT3-DNMT3L (ADD) domain. New studies show that the ADD domain is capable of sensing, and therefore integrating, the status of multiple histone modifications. This in turn dictates the in vivo localization or allosteric regulation of the full-length ADD-containing protein and its ability to function in downstream chromatin remodeling events. Strategies to re-engineer the ADD "reader pocket" in the de novo DNA methyltransferase DNMT3A such that it redirects this "writer" to new genomic loci proved useful in understanding important biological downstream consequences of mis-targeting of DNA methylation via altered reading of histone marks. Combined with genome-editing tools, this approach stands as a poof-of-principle and will be broadly applicable to the elucidation of epigenetic networks that have been altered by "reader" mutations, either artificially or as naturally occurs in some human diseases.
authors.affiliation: European Molecular Biology Laboratory , Genome Biology Unit, 69117 Heidelberg, Germany.
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Noh
authors.affiliation: Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University , New York, New York 10065, United States.
authors.forename: C David
authors.initials: CD
authors.lastname: Allis
authors.affiliation: MOE Key Laboratory of Protein Sciences, Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University , Beijing 100084, P.R. China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
mesh_terms: D042002:Chromatin Assembly and Disassembly; D019175:DNA Methylation / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000502:physiology*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans
chemical_list: D006657:Histones