| Title | A Highly Sensitive and Robust Method for Genome-wide 5hmC Profiling of Rare Cell Populations |
| Authors | Han, Dali Lu, Xingyu Shih, Alan H. Nie, Ji You, Qiancheng Xu, Meng Michelle Melnick, Ari M. Levine, Ross L. He, Chuan |
| Affiliation | Univ Chicago, Dept Chem, Dept Biochem & Mol Biol, Howard Hughes Med Inst, 929 East 57th St, Chicago, IL 60637 USA. Univ Chicago, Howard Hughes Med Inst, Inst Biophys Dynam, 929 East 57th St, Chicago, IL 60637 USA. Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10065 USA. Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. Mem Sloan Kettering Canc Ctr, Ctr Epigenet Res, New York, NY 10065 USA. Peking Univ, Coll Chem, MOE Key Lab Bioorgan Chem & Mol Engn, BNLMS, Beijing 100871, Peoples R China. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Weill Cornell Med Coll, Dept Med Hematol Oncol, New York, NY 10065 USA. Weill Cornell Med Coll, Dept Pharmacol, New York, NY 10065 USA. Cornell Univ, Weill Cornell Med Coll, 413 East 69th St,BB-1462, New York, NY 10021 USA. Univ Chicago, Dept Chem, Dept Biochem & Mol Biol, Howard Hughes Med Inst, 929 East 57th St, Chicago, IL 60637 USA. He, C (reprint author), Univ Chicago, Howard Hughes Med Inst, Inst Biophys Dynam, 929 East 57th St, Chicago, IL 60637 USA. Levine, RL (reprint author), Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10065 USA. Levine, RL (reprint author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. Levine, RL (reprint author), Mem Sloan Kettering Canc Ctr, Ctr Epigenet Res, New York, NY 10065 USA. |
| Keywords | DNA DEMETHYLATION DYNAMICS SINGLE-BASE RESOLUTION REGULATORY REGIONS MALIGNANT HEMATOPOIESIS TRANSCRIPTION FACTORS PROGENITOR CELLS STEM-CELLS LOW-INPUT CHIP-SEQ 5-HYDROXYMETHYLCYTOSINE |
| Issue Date | 2016 |
| Publisher | MOLECULAR CELL |
| Citation | MOLECULAR CELL.2016,63(4),711-719. |
| Abstract | We present a highly sensitive and selective chemical labeling and capture approach for genome-wide profiling of 5-hydroxylmethylcytosine (5hmC) using DNA isolated from similar to 1,000 cells (nano-hmC-Seal). Using this technology, we assessed 5hmC occupancy and dynamics across different stages of hematopoietic differentiation. Nano-hmC-Seal profiling of purified Tet2-mutant acute myeloid leukemia (AML) murine stem cells allowed us to identify leukemia-specific, differentially hydroxymethylated regions that harbor known and candidate disease-specific target genes with differential 5hmC peaks compared to normal stem cells. The change of 5hmC patterns in AML strongly correlates with differential gene expression, demonstrating the importance of dynamic alterations of 5hmC in regulating transcription in AML. Together, covalent 5hmC labeling offers an effective approach to study and detect DNA methylation dynamics in in vivo disease models and in limited clinical samples. |
| URI | http://hdl.handle.net/20.500.11897/491567 |
| ISSN | 1097-2765 |
| DOI | 10.1016/j.molcel.2016.06.028 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | å å¦ä¸ å å å·¥ç¨ å¦é ¢ 生物有机与分子工程教育部重点实验室 |
