Directional DNA Methylation Changes and Complex Intermediate States Accompany Lineage Specificity in the Adult Hematopoietic Compartment

Hodges, E., Molaro, A., Dos Santos, C. O., Thekkat, P., Song, Q., Uren, P. J., Park, J. H., Butler, J., Rafii, S., McCombie, W. R., Smith, A. D., Hannon, G. J. (2011) Directional DNA Methylation Changes and Complex Intermediate States Accompany Lineage Specificity in the Adult Hematopoietic Compartment. Molecular Cell, 44 (1). pp. 17-28. ISSN 1097-2765

URL: http://www.ncbi.nlm.nih.gov/pubmed/21924933
DOI: 10.1016/j.molcel.2011.08.026

Abstract

Summary DNA methylation has been implicated as an epigenetic component of mechanisms that stabilize cell-fate decisions. Here, we have characterized the methylomes of human female hematopoietic stem/progenitor cells (HSPCs) and mature cells from the myeloid and lymphoid lineages. Hypomethylated regions (HMRs) associated with lineage-specific genes were often methylated in the opposing lineage. In HSPCs, these sites tended to show intermediate, complex patterns that resolve to uniformity upon differentiation, by increased or decreased methylation. Promoter HMRs shared across diverse cell types typically display a constitutive core that expands and contracts in a lineage-specific manner to fine-tune the expression of associated genes. Many newly identified intergenic HMRs, both constitutive and lineage specific, were enriched for factor binding sites with an implied role in genome organization and regulation of gene expression, respectively. Overall, our studies represent an important reference data set and provide insights into directional changes in DNA methylation as cells adopt terminal fates.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA methylation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > epigenetics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > epigenetics

therapies > stem cells
CSHL Authors:
Communities: CSHL Cancer Center Shared Resources > Bioinformatics Service
CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL Cancer Center Shared Resources > Flow Cytometry Service
CSHL labs > Hannon lab
CSHL labs > McCombie lab
CSHL Cancer Center Program > Cancer Genetics
Depositing User: CSHL Librarian
Date Deposited: 09 Nov 2011 19:27
Last Modified: 14 Oct 2015 16:49
PMCID: PMC3412369
Related URLs:
URI: http://repository.cshl.edu/id/eprint/15645

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