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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

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)

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)

More...

GSM1607383	Dnmt3A Chip-Seq EpiSC
GSM1607384	Dnmt3B Chip-Seq EpiSC
GSM1607385	Input Dnmt3AB ChIP-Seq EpiSC

GSM1607386	H3K4me1 Chip-Seq EpiSC
GSM1607387	H3K27ac Chip-Seq EpiSC
GSM1607388	H3K4me3 Chip-Seq EpiSC
GSM1607389	MEDIP-Seq EpiSC
GSM1607390	HydroxyMedip-Seq EpiSC
GSM1607391	Input HydroxyMedip-Seq EpiSC
GSM1607392	Dnmt3A Chip-Seq KC
GSM1607393	Dnmt3B Chip-Seq KC
GSM1607394	Input Dnmt3AB Chip-Seq KC
GSM1607395	H3K4me1 Chip-Seq KC
GSM1607396	H3K27ac Chip-Seq KC
GSM1607397	H3K4me3 Chip-Seq KC
GSM1607398	MEDIP-Seq KC
GSM1607399	HydroxyMedip-Seq KC
GSM1607400	Input HydroxyMedip-Seq KC
GSM1607401	H3K4me3 shCTRL
GSM1607402	H3K4me3 shDNMT3A
GSM1607403	H3K4me3 shDNMT3B
GSM1607404	H3K27ac shCTRL
GSM1607405	H3K27ac shDNMT3A
GSM1607406	H3K27ac shDNMT3B
GSM1607407	MEDIP-SEQ shDNMT3B
GSM1607408	MEDIP-SEQ shDNMT3A
GSM1607409	MEDIP-SEQ shCTRL
GSM1607413	INPUT shCTRL
GSM1607414	INPUT shDNMT3A
GSM1607415	INPUT shDNMT3B
GSM1634323	RNA-Seq Undifferentiated EpSC Replicate1
GSM1634324	RNA-Seq Undifferentiated EpSC Replicate 2
GSM1634325	RNA-Seq Undifferentiated EpSC Replicate 3
GSM1634326	RNA-Seq Differentiated Keratinocytes Replicate1
GSM1634327	RNA-Seq Differentiated Keratinocytes Replicate2
GSM1634328	RNA-Seq Differentiated Keratinocytes Replicate3
GSM1634329	RNA-Seq Undifferentiated EpSC shCTRL Replicate 1
GSM1634330	RNA-Seq Undifferentiated EpSC shCTRL Replicate 2
GSM1634331	RNA-Seq Undifferentiated EpSC shCTRL Replicate 3
GSM1634332	RNA-Seq Undifferentiated EpSC shDNMT3A Replicate 1
GSM1634333	RNA-Seq Undifferentiated EpSC shDNMT3A Replicate 2
GSM1634334	RNA-Seq Undifferentiated EpSC shDNMT3A Replicate 3
GSM1634335	RNA-Seq Undifferentiated EpSC shDNMT3B Replicate 1
GSM1634336	RNA-Seq Undifferentiated EpSC shDNMT3B Replicate 2
GSM1634337	RNA-Seq Undifferentiated EpSC shDNMT3B Replicate 3
GSM2228897	H3K4me1 rep 2 Chip-Seq EpiSC
GSM2228898	H3K4me1 rep3 Chip-Seq EpiSC
GSM2228899	H3K27ac rep 2 Chip-Seq EpiSC
GSM2228900	H3K4me1 rep2 Chip-Seq KC
GSM2228901	H3K4me1 rep 3 Chip-Seq KC
GSM2228902	H3K27ac rep2 Chip-Seq KC
GSM2228903	H3K27ac rep3 Chip-Seq KC
GSM2228904	H3K36me3 Chip-Seq EpiSC
GSM2228905	H3K36me3 Chip-Seq KC
GSM2228906	HydroxyMedip Seq shCTRL
GSM2228907	HydroxyMedip Seq shDnmt3a
GSM2228908	HydroxyMedip Seq shDnmt3b
GSM2228909	Medip Seq ShCTRL
GSM2228910	Medip Seq shTET2
GSM2228911	Dnmt3a EpSC ChIp-seq replicate 2
GSM2228912	Dnmt3b EpSC ChIp-seq replicate 2
GSM2228913	shDnm3a Dnmt3a Chip-seq
GSM2228914	shDnm3b Dnmt3b Chip-seq
GSM2228915	shSETD2 Dnmt3a ChIP-seq
GSM2228916	shSETD2 Dnmt3b ChIP-seq

Relations

BioProject

SRA

Download family	Format
SOFT formatted family file(s)	SOFT
MINiML formatted family file(s)	MINiML
Series Matrix File(s)	TXT

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 Selector
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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