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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 14, 2014 |
| Title |
Divergent functions of hematopoietic transcription factors in lineage priming and differentiation during erythro-megakaryopoiesis |
| Organism |
Mus musculus |
| Experiment type |
Other
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| Summary |
Combinatorial actions of relatively few transcription factors control hematopoietic differentiation. To investigate this process in erythro-megakaryopoiesis, we correlated the genome-wide chromatin occupancy signatures of four master hematopoietic transcription factors (GATA1, GATA2, TAL1, and FLI1) and three diagnostic histone modification marks with the gene expression changes that occur during development of primary cultured megakaryocytes (MEG) and primary erythroblasts (ERY) from murine fetal liver hematopoietic stem/progenitor cells. We identified a robust, genome-wide mechanism of MEG-specific lineage priming by a previously described stem/progenitor cell-expressed transcription factor heptad (GATA2, LYL1, TAL1, FLI1, ERG, RUNX1, LMO2) binding to MEG-associated cis-regulatory modules (CRMs) in multipotential progenitors. This is followed by genome-wide GATA factor switching that mediates further induction of MEG-specific genes following lineage commitment. Interaction between GATA and ETS factors appears to be a key determinant of these processes. In contrast, ERY-specific lineage priming is biased toward GATA2-independent mechanisms. In addition to its role in MEG lineage priming, GATA2 plays an extensive role in late megakaryopoiesis as a transcriptional repressor at loci defined by a specific DNA signature. Our findings reveal important new insights into how ERY and MEG lineages arise from a common bipotential progenitor via overlapping and divergent functions of shared hematopoietic transcription factors.
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| Overall design |
Genome-wide chromatin occupancy using ChIP-seq on 4 transcription factors (GATA1, GATA2, TAL1, and FLII) and three histone marks (H3K4me1, H3K4me3, and H3K27me3) in lineage-commited primary erythoblasts (ERY) and primary cultured megakaryocytes (MEG).
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| Contributor(s) |
Pimkin M, Kossenkov AV, Mishra T, Morrissey CS, Wu W, Keller CA, Blobel GA, Lee D, Beer MA, Hardison RC, Weiss MJ |
| Citation(s) |
25319996 |
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| Submission date |
Oct 02, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
ENCODE DCC |
| E-mail(s) |
encode-help@lists.stanford.edu
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| Organization name |
ENCODE DCC
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| Street address |
300 Pasteur Dr
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| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305-5120 |
| Country |
USA |
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| Platforms (3) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (42)
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| Relations |
| BioProject |
PRJNA267254 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE51337_RAW.tar |
299.2 Gb |
(http)(custom) |
TAR (of BEDGRAPH, BIGWIG, BROADPEAK, CEL, TXT) |
SRA Run Selector |
| Processed data provided as supplementary file |
| Raw data provided as supplementary file |
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