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00925njm 22002777a 4500 dc Carrillo de SantaPau, Enrique author Juan, David author Pancaldi, Vera author Were, Felipe author Martin-Subero, Ignacio author Rico, Daniel author Valencia, Alfonso author 2017-09-19 Hematopoiesis is one of the best characterized biological systems but the connection between chromatin changes and lineage differentiation is not yet well understood. We have developed a bioinformatic workflow to generate a chromatin space that allows to classify 42 human healthy blood epigenomes from the BLUEPRINT, NIH ROADMAP and ENCODE consortia by their cell type. This approach let us to distinguish different cells types based on their epigenomic profiles, thus recapitulating important aspects of human hematopoiesis. The analysis of the orthogonal dimension of the chromatin space identify 32,662 chromatin determinant regions (CDRs), genomic regions with different epigenetic characteristics between the cell types. Functional analysis revealed that these regions are linked with cell identities. The inclusion of leukemia epigenomes in the healthy hematological chromatin sample space gives us insights on the healthy cell types that are more epigenetically similar to the disease samples. Further analysis of tumoral epigenetic alterations in hematopoietic CDRs points to sets of genes that are tightly regulated in leukemic transformations and commonly mutated in other tumors. Our method provides an analytical approach to study the relationship between epigenomic changes and cell lineage differentiation. Method availability: https://github.com/david-juan/ChromDet. Nucleic Acids Res.2017;45 (16): 9244-9259. 10.1093/nar/gkx618 1362-4962 0305-1048 Nucleic acids research 28934481 http://hdl.handle.net/20.500.12105/5061 CHROMATIN STATE DYNAMICS HUMAN CELL-TYPES STEM-CELLS LINEAGE COMMITMENT BONE-MARROW B-CELLS REGULATES DIFFERENTIATION MACROPHAGE ACTIVATION HISTONE MODIFICATIONS MYELOID PROGENITORS Automatic identification of informative regions with epigenomic changes associated to hematopoiesis