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Dnmt3a and Dnmt3b associate with enhancers to regulate human epidermal stem cell homeostasis

ABSTRACT: Here, we show that Dnmt3a and Dnmt3b show non-overlapping and unique patterns of genomic localization in human epidermal stem cells and their differentiated counterparts. Dnmt3a, but not Dnmt3b, binds to the TSSs of a cohort of genes required for the interaction of stem cells with their underlying stroma. Unexpectedly, TSSs bound by Dnmt3a are highly transcribed and are devoid of DNA-methylation. Conversely, Dnmt3b specifically decorates the genebody of genes that establish the stem cell and differentiated signatures. Genic occupation by Dnmt3b correlates with high levels of DNA-methylation, broad domains of histone H3K4me3 8, and robust transcription. Intriguingly, both proteins also bind to the most active subset of enhancers, and are required for the production of their associated bidirectional enhancer RNAs 9. We show that typical and super-enhancers are very dynamically regulated during the linear transition of epidermal stem cells to differentiated keratinocytes. Interestingly, Dnmt3a and Dnmt3b show a strong preference for the super-enhancers that define the ectodermal lineage, but importantly, that also establish the functional traits associated to the stem cell and differentiated states. These enhancers contain very low levels of DNA-methylation, but high amounts of DNA-hydroxymethylation. Depletion of either protein completely impairs human epidermal stem cell self-renewal by inducing their spontaneous differentiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE65838 | GEO | 2016/07/15

SECONDARY ACCESSION(S): PRJNA275188

REPOSITORIES: GEO

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Dnmt3a associates with promoters and enhancers to protect epidermal stem cells from cancer [RNA-seq]

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2020-04-07 | GSE92423 | GEO

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2020-03-26 | GSE92422 | GEO

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2017-06-13 | GSE92421 | GEO

Homo sapiens

Project description:Dnmt3a and Dnmt3b associate with enhancers to regulate human epidermal stem cell homeostasis

| PRJNA275188 | ENA

de novo DNA Methylation Balances Hematopoietic Stem Cell Self-Renewal and Differentiation

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Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation

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2015-01-22 | E-GEOD-57413 | biostudies-arrayexpress

Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation

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2015-01-20 | E-GEOD-57411 | biostudies-arrayexpress

Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation

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2015-01-20 | E-GEOD-57412 | biostudies-arrayexpress

DNA methylation analysis and expression profiling during murine embryogenesis and in embryos deficient for DNMT3A or DNMT3B

Project description:We quantified the targets and kinetics of DNA methylation acquisition in mouse embryos, and determined the contribution of the de novo methyltransferases DNMT3A and DNMT3B to this process. We provide single-base maps of cytosine methylation by RRBS from the blastocysts to post-implantation stages and in embryos lacking DNMT3A or DNMT3B activity, and performed RNA-Seq in embryos lacking DNMT3B activity. We sequenced RRBS libraries prepared from genomic DNA isolated from embryos at consecutive stages of development between E3.5 and E11.5,and adult differentiated cells (sperm, liver). We performed RRBS on blastocysts at E3.5/E4.5, dissected epiblasts at E5.5/E6.5/E7/5, whole embryos at E8.5/E10.5 and limbs at E11.5. RRBS experiments in Dnmt3a-/- and Dnmt3b-/- embryos were performed in biological duplicates on individual embryos. We sequenced RNA-Seq libraries prepared from total RNAs of three WT and Dnmt3b-/- littermate embryos collected at E8.5.

2014-11-14 | E-GEOD-60334 | biostudies-arrayexpress

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