title: Epigenetic regulation of hematopoiesis by DNA methylation.
abstract: During embryonic development, cell type-specific transcription factors promote cell identities, while epigenetic modifications are thought to contribute to maintain these cell fates. Our understanding of how genetic and epigenetic modes of regulation work together to establish and maintain cellular identity is still limited, however. Here, we show that DNA methyltransferase 3bb.1 (dnmt3bb.1) is essential for maintenance of hematopoietic stem and progenitor cell (HSPC) fate as part of an early Notch-runx1-cmyb HSPC specification pathway in the zebrafish. Dnmt3bb.1 is expressed in HSPC downstream from Notch1 and runx1, and loss of Dnmt3bb.1 activity leads to reduced cmyb locus methylation, reduced cmyb expression, and gradual reduction in HSPCs. Ectopic overexpression of dnmt3bb.1 in non-hematopoietic cells is sufficient to methylate the cmyb locus, promote cmyb expression, and promote hematopoietic development. Our results reveal an epigenetic mechanism supporting the maintenance of hematopoietic cell fate via DNA methylation-mediated perdurance of a key transcription factor in HSPCs.
authors.affiliation: Division of Developmental Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.
authors.forename: Aniket V
authors.initials: AV
authors.lastname: Gore
authors.affiliation: Division of Developmental Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.
authors.forename: Brett
authors.initials: B
authors.lastname: Athans
authors.affiliation: Program in Developmental Endocrinology and Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.
authors.forename: James R
authors.initials: JR
authors.lastname: Iben
authors.affiliation: Division of Developmental Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.
authors.forename: Kristin
authors.initials: K
authors.lastname: Johnson
authors.affiliation: Division of Developmental Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.
authors.forename: Valya
authors.initials: V
authors.lastname: Russanova
authors.affiliation: Division of Developmental Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Castranova
authors.affiliation: Division of Developmental Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.
authors.forename: Van N
authors.initials: VN
authors.lastname: Pham
authors.affiliation: Division of Developmental Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Butler
authors.affiliation: Division of Developmental Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Williams-Simons
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, United States.
authors.forename: James T
authors.initials: JT
authors.lastname: Nichols
authors.affiliation: Oncogenesis and Development Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, United States.
authors.forename: Erica
authors.initials: E
authors.lastname: Bresciani
authors.affiliation: Division of Developmental Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.
authors.forename: Bejamin
authors.initials: B
authors.lastname: Feldman
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, United States.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Kimmel
authors.affiliation: Oncogenesis and Development Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, United States.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Liu
authors.affiliation: Division of Developmental Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States.
authors.forename: Brant M
authors.initials: BM
authors.lastname: Weinstein
mesh_terms: D000818:Animals; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015870:Gene Expression; D005786:Gene Expression Regulation; D056426:Genetic Loci; D006410:Hematopoiesis / Q000502:physiology*; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish
chemical_list: D008780:Methyltransferases
keywords: Cell Fate maintenance; DNA methylation; Epigenetics; developmental biology; stem cells; zebrafish
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