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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
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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.
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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
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Contributor(s) |
Su J, Zhang X, Goodell MA, Park HJ |
Citation(s) |
27428748 |
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Submission date |
Aug 18, 2015 |
Last update date |
May 15, 2019 |
Contact name |
Jianzhong Su |
E-mail(s) |
jianzhongsu82@gmail.com
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Phone |
8322902241
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Organization name |
Baylor college of Medicine
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Street address |
1 Baylor Plaza
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City |
HOUSTON |
State/province |
TEXAS |
ZIP/Postal code |
77030 |
Country |
USA |
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Platforms (1) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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Samples (12)
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Relations |
BioProject |
PRJNA293214 |
SRA |
SRP062557 |