A promoter DNA demethylation landscape of human hematopoietic differentiation Calvanese, Vincenzo Fernández, Agustín F. Urdinguio, Rocío G. Suárez-Álvarez, Beatriz Mangas, Cristina Pérez-Gacía, Vicente Bueno, Clara Montes, Rosa Ramos-Mejia, Veronica Martínez Camblor, Pablo Ferrero, Cecilia Assenov, Yassen Bock, Christoph Menéndez, Pablo Carrera, Ana Clara López Larrea, Carlos Fraga, Mario F. P.M.'s Group is funded by The CICE (P08-CTS-3678 to P.M.) de la Junta de Andalucía, The FIS (PI070026 & PI100449) and The MICINN (PLE-2009-0111); Miguel Servet Program Fellowship (CP07/00059 to C.B.). The Marie Curie IIF (PIIF-GA-2009-236430 to V.R.-M.); ISCIII (CA10/01332 to R.M.); FPU Spanish Research Programme Fellowship (to V.C.); IUOPA (to A.F.F., R.G.U. and C.M.); Spanish Ministry of Health (PI061267; PS09/02454 to M.F.F. and PI080566 to C.L.L.); the Spanish National Research Council (CSIC; 200820I172 to M.F.F.); Community of Asturias (FYCIT IB09-106 to M.F.F.); Obra Social Cajastur, Spain (The IUOPA). Funding for open access charge: Spanish Ministry of Health (PS09/02454). 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. 2026-01-13T10:32:07Z 2026-01-13T10:32:07Z 2012 journal article Calvanese, V. et al. A promoter DNA demethylation landscape of human hematopoietic differentiation, Nucleic Acids Research, Volume 40, Issue 1, 1 January 2012, Pages 116–131, https://doi.org/10.1093/nar/gkr685 https://hdl.handle.net/10481/109604 10.1093/nar/gkr685 eng open access Oxford Academic