A highly sensitive and robust method for genome-wide 5hmC profiling of rare cell populations Journal Article


Authors: Han, D.; Lu, X.; Shih, A. H.; Nie, J.; You, Q.; Xu, M. M.; Melnick, A. M.; Levine, R. L.; He, C.
Article Title: A highly sensitive and robust method for genome-wide 5hmC profiling of rare cell populations
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 ∼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. © 2016 Elsevier Inc.
Journal Title: Molecular Cell
Volume: 63
Issue: 4
ISSN: 1097-2765
Publisher: Cell Press  
Date Published: 2016-08-18
Start Page: 711
End Page: 719
Language: English
DOI: 10.1016/j.molcel.2016.06.028
PROVIDER: scopus
PMCID: PMC4992443
PUBMED: 27477909
DOI/URL:
Notes: Article -- Export Date: 6 December 2016 -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Alan H Shih
    59 Shih
  2. Ross Levine
    775 Levine