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Series GSE65838 Query DataSets for GSE65838
Status Public on Jul 15, 2016
Title Dnmt3a and Dnmt3b associate with enhancers to regulate human epidermal stem cell homeostasis
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary 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.
Overall design Examination of genome wide localization of Dnmt3A and Dnmt3B and their overlap within genomic regulatory regions in a DNA-methylation dependent and independent manner. Genome wide total RNA quantification of Wild Type Human EpiSC and its Differentiated counterparts.
Contributor(s) Rinaldi L, Datta D, Serrat J, Morey L, Solanas G, Avgustinova A, Blanco E, Pons JI, Gomez D, Von Kriegsheim A, di Croce L, Benitah SA
Citation(s) 27476967
Submission date Feb 11, 2015
Last update date May 15, 2019
Contact name Debayan Datta
Organization name IRB Barcelona
Department Oncology
Lab Stem Cells and Cancer
Street address C. Baldiri Reixac 10
City Barcelona
State/province Barcelona
ZIP/Postal code 08028
Country Spain
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (65)
GSM1607383 Dnmt3A Chip-Seq EpiSC
GSM1607384 Dnmt3B Chip-Seq EpiSC
GSM1607385 Input Dnmt3AB ChIP-Seq EpiSC
BioProject PRJNA275188
SRA SRP054246

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE65838_RAW.tar 57.3 Mb (http)(custom) TAR (of BED)
GSE65838_RNAseq_UNDIFF_DIFF_fpkm.txt.gz 678.5 Kb (ftp)(http) TXT
GSE65838_RNAseq_shCTRL_sh3A_sh3B_fpkm.txt.gz 969.9 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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