Journal Article

A promoter DNA demethylation landscape of human hematopoietic differentiation

Vincenzo Calvanese, Agustín F. Fernández, Rocío G. Urdinguio, Beatriz Suárez-Alvarez, Cristina Mangas, Vicente Pérez-García, Clara Bueno, Rosa Montes, Verónica Ramos-Mejía, Pablo Martínez-Camblor, Cecilia Ferrero, Yassen Assenov, Christoph Bock, Pablo Menendez, Ana Clara Carrera, Carlos Lopez-Larrea and Mario F. Fraga

in Nucleic Acids Research

Volume 40, issue 1, pages 116-131
Published in print January 2012 | ISSN: 0305-1048
Published online September 2011 | e-ISSN: 1362-4962 | DOI: http://dx.doi.org/10.1093/nar/gkr685

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Global mechanisms defining the gene expression programs specific for hematopoiesis are still not fully understood. Here, we show that promoter DNA demethylation is associated with the activation of hematopoietic-specific genes. Using genome-wide promoter methylation arrays, we identified 694 hematopoietic-specific genes repressed by promoter DNA methylation in human embryonic stem cells and whose loss of methylation in hematopoietic can be associated with gene expression. The association between promoter methylation and gene expression was studied for many hematopoietic-specific genes including CD45, CD34, CD28, CD19, the T cell receptor (TCR), the MHC class II gene HLA-DR, perforin 1 and the phosphoinositide 3-kinase (PI3K) and results indicated that DNA demethylation was not always sufficient for gene activation. Promoter demethylation occurred either early during embryonic development or later on during hematopoietic differentiation. Analysis of the genome-wide promoter methylation status of induced pluripotent stem cells (iPSCs) generated from somatic CD34+ HSPCs and differentiated derivatives from CD34+ HSPCs confirmed the role of DNA methylation in regulating the expression of genes of the hemato-immune system, and indicated that promoter methylation of these genes may be associated to stemness. Together, these data suggest that promoter DNA demethylation might play a role in the tissue/cell-specific genome-wide gene regulation within the hematopoietic compartment.

Journal Article.  8353 words.  Illustrated.

Subjects: Chemistry ; Biochemistry ; Bioinformatics and Computational Biology ; Genetics and Genomics ; Molecular and Cell Biology

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