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| Status |
Public on Dec 09, 2015 |
| Title |
Epigenetic Program and Transcription Factor Circuitry of Dendritic Cell Development |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Dendritic cells (DC) are professional antigen presenting cells that develop from hematopoietic stem cells through successive steps of lineage commitment and differentiation. Multipotent progenitors (MPP) are committed to DC restricted common DC progenitors (CDP), which differentiate into specific DC subsets, classical DC (cDC) and plasmacytoid DC (pDC). To determine epigenetic states and regulatory circuitries during DC differentiation, we measured consecutive changes of genome-wide gene expression, histone modification and transcription factor occupancy during the sequel MPP-CDP-cDC/pDC. Specific histone marks in CDP reveal a DC-primed epigenetic signature, which is maintained and reinforced during DC differentiation. Epigenetic marks and transcription factor PU.1 occupancy increasingly coincide upon DC differentiation. By integrating PU.1 occupancy and gene expression we devised a transcription factor regulatory circuitry for DC commitment and subset specification. The circuitry provides the transcription factor hierarchy that drives the sequel MPP-CDP-cDC/pDC, including Irf4, Irf8, Tcf4, Spib and Stat factors. The circuitry also includes feedback loops inferred for individual or multiple factors, which stabilize distinct stages of DC development and DC subsets. In summary, here we describe the basic regulatory circuitry of transcription factors that drives DC development.
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| Overall design |
H3K4me3, H3K9me3 and H3K27me3 occupancy in MPP, CDP, cDC and pDC.
The ChIP-seq profiles are visualized by a customized UCSC genome browser track hub (http://www.molcell.rwth-aachen.de/dc/).
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| Contributor(s) |
Lin Q, Chauvistré H, Costa IG, Gusmão EG, Mitzka S, Haenzelmann S, Baying B, Klisch T, Moriggl R, Hennuy B, Smeets H, Hoffmann K, Benes V, Seré K, Zenke M |
| Citation(s) |
26476451 |
| Submission date |
Jan 07, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Martin Zenke |
| E-mail(s) |
Martin.Zenke@rwth-aachen.de
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| Phone |
+49-241-80 80760
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| Organization name |
Institute for Biomedical Engineering
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| Department |
Cell Biology
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| Street address |
Universitatsklinikum Aachen, RWTH
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| City |
Aachen |
| State/province |
NRW |
| ZIP/Postal code |
52074 |
| Country |
Germany |
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| Platforms (2) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA271821 |
| SRA |
SRP051906 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE64767_RAW.tar |
2.8 Gb |
(http)(custom) |
TAR (of WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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