title: Towards understanding methyllysine readout.
abstract: BACKGROUND
  Lysine methylation is the most versatile covalent posttranslational modification (PTM) found in histones and non-histone proteins. Over the past decade a number of methyllysine-specific readers have been discovered and their interactions with histone tails have been structurally and biochemically characterized. More recently innovative experimental approaches have emerged that allow for studying reader interactions in the context of the full nucleosome and nucleosomal arrays.
  
  
  METHODS
  In this review we give a brief overview of the known mechanisms of histone lysine methylation readout, summarize progress recently made in exploring interactions with methylated nucleosomes, and discuss the latest advances in the development of small molecule inhibitors of the methyllysine-specific readers.
  
  
  CONCLUSIONS
  New studies reveal various reader-nucleosome contacts outside the methylated histone tail, thus offering a better model for association of histone readers to chromatin and broadening our understanding of the functional implications of these interactions. In addition, some progress has been made in the design of antagonists of these interactions.
  
  
  CONCLUSIONS
  Specific lysine methylation patterns are commonly associated with certain chromatin states and genomic elements, and are linked to distinct biological outcomes such as transcription activation or repression. Disruption of patterns of histone modifications is associated with a number of diseases, and there is tremendous therapeutic potential in targeting histone modification pathways. Thus, investigating binding of readers of these modifications is not only important for elucidating fundamental mechanisms of chromatin regulation, but also necessary for the design of targeted therapeutics. This article is part of a Special Issue entitled: Molecular mechanisms of histone modification function.
authors.affiliation: Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA. Electronic address: catherine-musselman@uiowa.edu.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Musselman
authors.affiliation: Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL 32827, USA.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Khorasanizadeh
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Kutateladze
mesh_terms: D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008958:Models, Molecular; D009707:Nucleosomes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D009707:Nucleosomes; D054852:Small Molecule Libraries; D014157:Transcription Factors; D008239:Lysine
keywords: Histone; Histone reader; Inhibitor; Methyllysine; Nucleosome
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