Epigenetic regulation of hematopoiesis by DNA methylation

ELife
Aniket V GoreBrant M Weinstein

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.

References

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Citations

Apr 12, 2017·ELife·Marina Venero GalanternikBrant M Weinstein
Feb 13, 2018·Wiley Interdisciplinary Reviews. Developmental Biology·Aniket V GoreBrant M Weinstein
May 29, 2018·Nature Ecology & Evolution·Aniket V GoreBrant M Weinstein
Apr 6, 2017·BMC Molecular Biology·Shubham GoyalHarukazu Suzuki
Apr 7, 2019·Biochemical Society Transactions·Julia A Horsfield
Sep 21, 2018·Frontiers in Genetics·Alberto Rissone, Shawn M Burgess
Aug 10, 2019·Nature Communications·Florian BonkhoferRoger Patient
Jan 16, 2021·Angiogenesis·Leah J Greenspan, Brant M Weinstein
Feb 20, 2021·Briefings in Functional Genomics·Veronica Bergo, Eirini Trompouki

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Datasets Mentioned

BETA
GSE74929

Methods Mentioned

BETA
genotyping
transgenic
Fluorescence Activated Cell Sorting
RRBS
RNAseq
RNA seq
immunoprecipitation
ChIP
flow cytometry
PCR

Software Mentioned

TOPHAT
Trimmomatic
Ingenuity
Cufflinks
WashU epigenetics browser
SOLiD
Bismark
PARTEK
SMARTer
UCSC genome browser

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