Large conserved domains of low DNA methylation maintained by 5-hydroxymethycytosine and Dnmt3a
Cited 58 times inCited 51 times in
- Large conserved domains of low DNA methylation maintained by 5-hydroxymethycytosine and Dnmt3a
- Jeong, Mira; Sun, Deqiang; Luo, Min; Huang, Yun; Challen, Grant A; Rodriguez, Benjamin; Zhang, Xiaotian; Chavez, Lukas; Wang, Hui; Hannah, Rebecca; Kim, Sang-Bae; Yang, Liubin; Ko, Myung Gon; Chen, Rui; Gottgens, Berthold; Lee, Ju-Seog; Gunaratne, Preethi; Godley, LA; Darlington, GJ; Rao, Anjana; Li, Wei; Goodell, Margaret A
- Issue Date
- NATURE PUBLISHING GROUP
- NATURE GENETICS, v.46, no.1, pp.17 - 23
- Gains and losses in DNA methylation are prominent features of mammalian cell types. To gain insight into the mechanisms that promote shifts in DNA methylation and contribute to changes in cell fate, including malignant transformation, we performed genome-wide mapping of 5-methylcytosine and 5-hydroxymethylcytosine in purified mouse hematopoietic stem cells. We discovered extended regions of low methylation (canyons) that span conserved domains frequently containing transcription factors and are distinct from CpG islands and shores. About half of the genes in these methylation canyons are coated with repressive histone marks, whereas the remainder are covered by activating histone marks and are highly expressed in hematopoietic stem cells (HSCs). Canyon borders are demarked by 5-hydroxymethylcytosine and become eroded in the absence of DNA methyltransferase 3a (Dnmt3a). Genes dysregulated in human leukemias are enriched for canyon-associated genes. The new epigenetic landscape we describe may provide a mechanism for the regulation of hematopoiesis and may contribute to leukemia development. © 2014 Nature America, Inc.
- Appears in Collections:
- BIO_Journal Papers
- Files in This Item:
- There are no files associated with this item.
can give you direct access to the published full text of this article. (UNISTARs only)
Show full item record
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.