title: Changes of 5-hydroxymethylcytosine distribution during myeloid and lymphoid differentiation of CD34+ cells.
abstract: BACKGROUND
  Hematopoietic stem cell renewal and differentiation are regulated through epigenetic processes. The conversion of 5-methylcytosine into 5-hydroxymethylcytosine (5hmC) by ten-eleven-translocation enzymes provides new insights into the epigenetic regulation of gene expression during development. Here, we studied the potential gene regulatory role of 5hmC during human hematopoiesis.
  
  
  RESULTS
  We used reduced representation of 5-hydroxymethylcytosine profiling (RRHP) to characterize 5hmC distribution in CD34+ cells, CD4+ T cells, CD19+ B cells, CD14+ monocytes and granulocytes. In all analyzed blood cell types, the presence of 5hmC at gene bodies correlates positively with gene expression, and highest 5hmC levels are found around transcription start sites of highly expressed genes. In CD34+ cells, 5hmC primes for the expression of genes regulating myeloid and lymphoid lineage commitment. Throughout blood cell differentiation, intragenic 5hmC is maintained at genes that are highly expressed and required for acquisition of the mature blood cell phenotype. Moreover, in CD34+ cells, the presence of 5hmC at enhancers associates with increased binding of RUNX1 and FLI1, transcription factors essential for hematopoiesis.
  
  
  CONCLUSIONS
  Our study provides a comprehensive genome-wide overview of 5hmC distribution in human hematopoietic cells and new insights into the epigenetic regulation of gene expression during human hematopoiesis.
authors.affiliation: Nordic European Molecular Laboratory (EMBL) Partnership, Centre for Molecular Medicine Norway, University of Oslo, Blindern, P.O. Box 1137, 0318 Oslo, Norway ; Department of Genetics, Institute for Cancer Research, Oslo University Hospital - The Norwegian Radium Hospital, Oslo, Norway.
authors.forename: Xavier
authors.initials: X
authors.lastname: Tekpli
authors.affiliation: Nordic European Molecular Laboratory (EMBL) Partnership, Centre for Molecular Medicine Norway, University of Oslo, Blindern, P.O. Box 1137, 0318 Oslo, Norway ; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Urbanucci
authors.affiliation: Nordic European Molecular Laboratory (EMBL) Partnership, Centre for Molecular Medicine Norway, University of Oslo, Blindern, P.O. Box 1137, 0318 Oslo, Norway.
authors.forename: Adnan
authors.initials: A
authors.lastname: Hashim
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Cathrine B
authors.initials: CB
authors.lastname: Vågbø
authors.affiliation: Department of Medical Genetics, University of Oslo, Oslo University Hospital, Oslo, Norway.
authors.forename: Robert
authors.initials: R
authors.lastname: Lyle
authors.affiliation: Department of Pharmacology, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Marianne K
authors.initials: MK
authors.lastname: Kringen
authors.affiliation: Department of Obstetrics and Gynecology, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Anne Cathrine
authors.initials: AC
authors.lastname: Staff
authors.affiliation: Department of Haematology, Oslo University Hospital, Oslo, Norway.
authors.forename: Ingunn
authors.initials: I
authors.lastname: Dybedal
authors.affiliation: Nordic European Molecular Laboratory (EMBL) Partnership, Centre for Molecular Medicine Norway, University of Oslo, Blindern, P.O. Box 1137, 0318 Oslo, Norway ; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway ; PCUK Movember Centre of Excellence, CCRCB, Queen's University, Belfast, UK.
authors.forename: Ian G
authors.initials: IG
authors.lastname: Mills
authors.affiliation: Clinic for Diagnostics and Intervention, Institute of Medical Microbiology, Oslo University Hospital, University of Oslo, Oslo, Norway ; Norwegian Center for Stem Cell Research, University of Oslo, Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Klungland
authors.affiliation: Nordic European Molecular Laboratory (EMBL) Partnership, Centre for Molecular Medicine Norway, University of Oslo, Blindern, P.O. Box 1137, 0318 Oslo, Norway ; Department of Haematology, Oslo University Hospital, Oslo, Norway ; Norwegian Center for Stem Cell Research, University of Oslo, Oslo, Norway.
authors.forename: Judith
authors.initials: J
authors.lastname: Staerk
keywords: 5-Hydroxymethylcytosine; Epigenetics; FLI1; Hematopoiesis; RUNX