title: The cysteine-rich domain of TET2 binds preferentially to mono- and dimethylated histone H3K36.
abstract: Missense mutations in Ten-eleven translocation 2 (TET2) gene are frequently found in leukaemia patients. Although mutations span the entire coding region, they tend to cluster in the C-terminal enzymatic domain and a cysteine-rich (CR) domain of unknown function. Herein, we found the CR domain binds chromatin preferentially at the histone H3 tail by recognising H3 lysine 36 mono- and dimethylation (H3K36me1/2). Importantly, missense mutations in the CR domain perturbed TET2 recruitment to the target locus and its enzymatic activities. Our findings identify a novel H3K36me recognition domain and uncover a critical link between histone modification and DNA hydroxylation in leukaemogenesis.
authors.affiliation: Division of Newborn Medicine, Children's Hospital Boston.|Department of Cell Biology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.|Organization for Research Initiatives and Development, Doshisha University.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Yamagata
authors.affiliation: Laboratory for Genetic Code, Graduate School of Life and Medical Sciences, Doshisha University, 1-3 Tatara Miyakodani, Kyotanabe 610-0394, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kobayashi
mesh_terms: D001665:Binding Sites / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D003545:Cysteine / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D049308:Dioxygenases; D057809:HEK293 Cells; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D008745:Methylation; D018613:Microscopy, Confocal; D008958:Models, Molecular; D020125:Mutation, Missense; D011485:Protein Binding; D000072417:Protein Domains; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C541081:TET2 protein, human; D008239:Lysine; D003545:Cysteine
keywords: TET2; epigenetics; histone H3K36 methylation; histones < chromosomes; leukaemia