ZFIN ID: ZDB-PUB-160128-4
Epigenetic regulation of hematopoiesis by DNA methylation
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.
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
Microarrays: GEO:GSE74929
MeSH Terms: Animals; DNA Methylation*; Epigenesis, Genetic*; Gene Expression; Gene Expression Regulation* (all 10) expand
PubMed: 26814702 Full text @ Elife
FIGURES   (current status)
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.