Yamagata, KazuyukiKobayashi, Akira2017-06-152017Yamagata, Kazuyuki, and Akira Kobayashi. 2017. “The cysteine-rich domain of TET2 binds preferentially to mono- and dimethylated histone H3K36.” Journal of Biochemistry 161 (4): 327-330. doi:10.1093/jb/mvx004. http://dx.doi.org/10.1093/jb/mvx004.http://nrs.harvard.edu/urn-3:HUL.InstRepos:33029837Missense 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.en-USepigeneticsTET2leukaemiahistone H3K36 methylationhistones < chromosomesJournal Article2017-06-1510.1093/jb/mvx004