PUBLICATION

Epigenetic regulation of hematopoiesis by DNA methylation

Authors
Gore, A.V., Athans, B., Iben, J.R., Johnson, K., Russanova, V., Castranova, D., Pham, V.N., Butler, M.G., Williams-Simons, L., Nichols, J.T., Bresciani, E., Feldman, B., Kimmel, C.B., Liu, P.P., Weinstein, B.M.
ID
ZDB-PUB-160128-4
Date
2016
Source
eLIFE   5: e11813 (Journal)
Registered Authors
Bresciani, Erica, Butler, Matthew, Castranova, Dan, Feldman, Benjamin, Gore, Aniket, Kimmel, Charles B., Liu, Pu Paul, Nichols, James Tucker, Pham, Van, Weinstein, Brant M.
Keywords
Cell Fate maintenance, DNA methylation, Epigenetics, developmental biology, stem cells, zebrafish
Datasets
GEO:GSE74929
MeSH Terms
  • Gene Expression Regulation*
  • Hematopoiesis/physiology*
  • Methyltransferases/genetics
  • Methyltransferases/metabolism
  • Zebrafish
  • Epigenesis, Genetic*
  • Animals
  • Gene Expression
  • DNA Methylation*
  • Genetic Loci
(all 10)
PubMed
26814702 Full text @ Elife
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.
Genes / Markers
Figures
Figure Gallery (10 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
EKW + MO2-dnmt3bb.1standard conditionsLong-pec
EKW + MO2-dnmt3bb.1standard conditionsProtruding-mouth
EKW + MO2-dnmt3bb.1standard conditionsDay 5
EKW + MO2-dnmt3bb.1standard conditionsDay 5 to Days 7-13
EKW + MO6-runx1standard conditionsPrim-25
EKW + MO6-runx1standard conditionsPrim-25
dnmt3bb.1y258/y258standard conditionsPrim-25
dnmt3bb.1y258/y258standard conditionsProtruding-mouth
dnmt3bb.1y258/y258standard conditionsProtruding-mouth
dnmt3bb.1y258/y258standard conditionsDay 4
1 - 10 of 32
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b1237
    		Small Deletion
    cz1TgTransgenic Insertion
      hg1
        		Point Mutation
        ta52b
          		Point Mutation
          y1TgTransgenic Insertion
            y258
              		Small Deletion
              y278TgTransgenic Insertion
                zf169TgTransgenic Insertion
                  1 - 8 of 8
                  Show
                  Human Disease / Model
                  No data available
                  Sequence Targeting Reagents
                  Target Reagent Reagent Type
                  dnmt3bb.1MO1-dnmt3bb.1MRPHLNO
                  dnmt3bb.1MO2-dnmt3bb.1MRPHLNO
                  dnmt3bb.1MO3-dnmt3bb.1MRPHLNO
                  dnmt3bb.1TALEN1-dnmt3bb.1TALEN
                  mybMO2-mybMRPHLNO
                  runx1MO6-runx1MRPHLNO
                  1 - 6 of 6
                  Show
                  Fish
                  Fish
                  dnmt3bb.1y258/y258
                  EKW
                  EKW + MO2-dnmt3bb.1
                  EKW + MO6-runx1
                  mib1ta52b/ta52b
                  runx1hg1/hg1
                  WT
                  y278Tg; zf169Tg + MO2-dnmt3bb.1
                  zf169Tg + MO2-dnmt3bb.1
                  1 - 9 of 9
                  Show
                  Antibodies
                  No data available
                  Orthology
                  Gene Orthology
                  dnmt3bb.1
                  1 - 1 of 1
                  Show
                  Engineered Foreign Genes
                  Marker Marker Type Name
                  EGFPEFGEGFP
                  mAppleEFGmApple
                  1 - 2 of 2
                  Show
                  Mapping
                  No data available
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                  Citation
                  Gore, A.V., Athans, B., Iben, J.R., Johnson, K., Russanova, V., Castranova, D., Pham, V.N., Butler, M.G., Williams-Simons, L., Nichols, J.T., Bresciani, E., Feldman, B., Kimmel, C.B., Liu, P.P., Weinstein, B.M. (2016) Epigenetic regulation of hematopoiesis by DNA methylation. eLIFE. 5:e11813.