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Updated: May 5, 2026

Immunostaining for DNA Modifications: Computational Analysis of Confocal Images
Published on: September 7, 2017
Large conserved domains of low DNA methylation maintained by Dnmt3a
Mira Jeong1, Deqiang Sun2, Min Luo1
11] Stem Cells and Regenerative Medicine Center, Department of Pediatrics and Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, USA. [2].
None:
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.
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