title: Directional DNA methylation changes and complex intermediate states accompany lineage specificity in the adult hematopoietic compartment.
abstract: DNA methylation has been implicated as an epigenetic component of mechanisms that stabilize cell-fate decisions. Here, we have characterized the methylomes of human female hematopoietic stem/progenitor cells (HSPCs) and mature cells from the myeloid and lymphoid lineages. Hypomethylated regions (HMRs) associated with lineage-specific genes were often methylated in the opposing lineage. In HSPCs, these sites tended to show intermediate, complex patterns that resolve to uniformity upon differentiation, by increased or decreased methylation. Promoter HMRs shared across diverse cell types typically display a constitutive core that expands and contracts in a lineage-specific manner to fine-tune the expression of associated genes. Many newly identified intergenic HMRs, both constitutive and lineage specific, were enriched for factor binding sites with an implied role in genome organization and regulation of gene expression, respectively. Overall, our studies represent an important reference data set and provide insights into directional changes in DNA methylation as cells adopt terminal fates.
authors.affiliation: Watson School of Biological Sciences, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Hodges
authors.forename: Antoine
authors.initials: A
authors.lastname: Molaro
authors.forename: Camila O
authors.initials: CO
authors.lastname: Dos Santos
authors.forename: Pramod
authors.initials: P
authors.lastname: Thekkat
authors.forename: Qiang
authors.initials: Q
authors.lastname: Song
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Uren
authors.forename: Jin
authors.initials: J
authors.lastname: Park
authors.forename: Jason
authors.initials: J
authors.lastname: Butler
authors.forename: Shahin
authors.initials: S
authors.lastname: Rafii
authors.forename: W Richard
authors.initials: WR
authors.lastname: McCombie
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Smith
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
mesh_terms: D000328:Adult; D001665:Binding Sites; D002454:Cell Differentiation; D019070:Cell Lineage; D055028:Comparative Genomic Hybridization; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D015894:Genome, Human; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006413:Hematopoietic System; D006801:Humans; D008954:Models, Biological; D011401:Promoter Regions, Genetic