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A promoter DNA demethylation landscape of human hematopoietic differentiation

ABSTRACT: Global mechanisms defining the gene expression programs specific for hematopoiesis are still not fully understood. Here, we show that promoter DNA demethylation is associated 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 ESCs 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. Total DNA isolated by standard procedures from different primary samples corresponding to healthy patients and several cell lines.

ORGANISM(S): Homo sapiens

SUBMITTER: Agustin Fernandez

PROVIDER: E-GEOD-30090 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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A promoter DNA demethylation landscape of human hematopoietic differentiation.

Calvanese Vincenzo V Fernández Agustín F AF Urdinguio Rocío G RG Suárez-Alvarez Beatriz B Mangas Cristina C Pérez-García Vicente V Bueno Clara C Montes Rosa R Ramos-Mejía Verónica V Martínez-Camblor Pablo P Martínez-Camblor Pablo P Ferrero Cecilia C Assenov Yassen Y Bock Christoph C Menendez Pablo P Carrera Ana Clara AC Lopez-Larrea Carlos C Fraga Mario F MF

Nucleic acids research 20110912 1

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 ...[more]

PMID: 21911366

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A promoter DNA demethylation landscape of human hematopoietic differentiation

Publications

A promoter DNA demethylation landscape of human hematopoietic differentiation.

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