Epigenetic regulation of hematopoiesis by DNA methylation

• DOI: 10.7554/elife.11813
• Publication Date: 2016-01-26T09:00:49Z
• Authors: Aniket V Gore; Brett Athans; James R Iben; Kristin Johnson; Valya Russanova; Daniel Castranova; Van N Pham; Matthew G Butler; Lisa Williams-Simons; James T Nichols; Erica Bresciani; Bejamin Feldman; Charles B Kimmel; Paul P Liu; Brant M Weinstein
• Keywords: RUNX1; Ectopic expression; Cell fate determination

During embryonic development, cell type-specific transcription factors promote identities, while epigenetic modifications are thought to contribute maintain these fates. Our understanding of how genetic and modes regulation work together establish cellular identity is still limited, however. Here, we show that DNA methyltransferase 3bb.1 (dnmt3bb.1) essential for maintenance hematopoietic stem progenitor (HSPC) fate as part an early Notch-runx1-cmyb HSPC specification pathway in the zebrafish. Dnmt3bb.1 expressed downstream from Notch1 runx1, loss activity leads reduced cmyb locus methylation, expression, gradual reduction HSPCs. Ectopic overexpression dnmt3bb.1 non-hematopoietic cells sufficient methylate locus, development. results reveal mechanism supporting via methylation-mediated perdurance a key factor