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Series GSE72148 Query DataSets for GSE72148
Status Public on May 20, 2016
Title DNMT3A and TET2 Compete and Cooperate to Repress Differentiation Lineage-Specific Factors in Hematopoietic Stem Cells
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Mutations in the epigenetic modifiers DNMT3A and TET2 non-randomly co-occur in lymphoma and leukemia despite their epistasis in the methylation-hydroxymethylation pathway. Using double knock-out (DKO) mice in which malignancy development is accelerated, we show that the DKO methylome reflects regions of independent, competitive and cooperative activity. Expression of lineage-specific transcription factors, including the erythroid regulator Klf1 is upregulated in DKO HSCs. DNMT3A and TET2 both repress Klf1 suggesting a model of cooperative inhibition by the epigenetic modifiers. These data demonstrate a dual role for TET2 in promoting and inhibiting HSC differentiation, loss of which, along with DNMT3A, obstructs differentiation leading to transformation.
 
Overall design I)Whole genome bisulfite sequencing of Tet2 conditional knockout hematopoietic stem cells, Tet2 and DNMT3a double knockout hematopoietic stem cells using Illumina HiSeq 2000.II)Whole genome CMS-enriched bisulfite sequencing of Tet2 conditional knockout hematopoietic stem cells, Tet2 and DNMT3a double knockout hematopoietic stem cells using Illumina HiSeq 2000.III)Whole genome mRNA profiles of Tet2 conditional knockout hematopoietic stem cells, Tet2 and DNMT3a double knockout hematopoietic stem cells using Illumina HiSeq 2000. IV)Genome wide histone modification H3K27me3 profiling of Tet2 conditional knockout hematopoietic stem cells, Tet2 and DNMT3a double knockout hematopoietic stem cells using Illumina HiSeq 2000
 
Contributor(s) Su J, Zhang X, Goodell MA, Park HJ
Citation(s) 27428748
Submission date Aug 18, 2015
Last update date May 15, 2019
Contact name Jianzhong Su
E-mail(s) jianzhongsu82@gmail.com
Phone 8322902241
Organization name Baylor college of Medicine
Street address 1 Baylor Plaza
City HOUSTON
State/province TEXAS
ZIP/Postal code 77030
Country USA
 
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (12)
GSM1856076 Tet2KO r1 RNAseq
GSM1856077 Tet2KO r2 RNAseq
GSM1856078 Tet2_3aDKO r1 RNAseq
Relations
BioProject PRJNA293214
SRA SRP062557

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE72148_RAW.tar 1.1 Gb (http)(custom) TAR (of BED, BW, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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