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| Status |
Public on Jun 27, 2013 |
| Title |
Pruning of the adipocyte cistrome by hematopoietic master regulator PU.1 (expression) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Master transcription factors are the gatekeepers of lineage identity. As such, they have been a major focus of efforts to manipulate cell fate for therapeutic purposes. The ETS transcription factor PU.1 has a potent ability to confer macrophage phenotypes on cells already committed to a different lineage, but how it overcomes the presence of other master regulators is not known. The nuclear receptor PPARγ is the master regulator of the adipose lineage, and its genomic binding pattern is well characterized in adipocytes. Here, we show that when expressed at macrophage levels in mature adipocytes, PU.1 bound a large fraction of its macrophage sites, where it induced chromatin opening and the expression of macrophage target genes. Strikingly, PU.1 markedly reduced the genomic binding of PPARγ without changing its abundance. PU.1 expression repressed genes with nearby adipocyte-specific PPARγ binding sites, while a common macrophage-adipocyte gene expression program was retained. Together, these data reveal unexpected lability within the adipocyte PPARγ cistrome and show that even in terminally differentiated cells, PU.1 can remodel the cistrome of another master regulator.
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| Overall design |
Microarray expression profiling was performed on 3T3-L1 adipocytes from two treatment groups: (1) adipocytes transduced with a control adenovirus expressing beta-galactosidase (LACZ-Ads) and (2) adipocytes transduced with an adenovirus expressing full-length murine PU.1 cDNA (PU.1-Ads). Each sample group consists of four biological replicates which are here defined as separate differentiations of mature 3T3-L1 adipocytes and adenoviral infections. Each replicate was hybridized to an individual array for a total of eight arrays.
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| Contributor(s) |
DiSpirito JR, Fang B, Wang F, Lazar MA |
| Citation(s) |
23775123 |
| Submission date |
Jun 26, 2013 |
| Last update date |
Feb 02, 2018 |
| Contact name |
Joanna R DiSpirito |
| E-mail(s) |
rdo2@mail.med.upenn.edu
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| Organization name |
University of Pennsylvania
|
| Department |
IDOM
|
| Lab |
Mitchell A. Lazar
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| Street address |
Smilow Center for Translational Research, 3400 Civic Center Boulevard
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
| GPL10787 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE48345 |
Pruning of the adipocyte cistrome by hematopoietic master regulator PU.1 |
|
| Relations |
| BioProject |
PRJNA209729 |
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