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| Status |
Public on May 27, 2011 |
| Title |
MAP3K4/CBP Regulated H2B acetylation Controls Epithelial-Mesenchymal Transition in Trophoblast Stem Cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Epithelial stem cells self-renew while maintaining multipotency, but the dependence of stem cell properties on maintenance of the epithelial phenotype is unclear. We previously showed that trophoblast stem (TS) cells lacking the protein kinase MAP3K4 maintain properties of both stemness and epithelial-mesenchymal transition (EMT). Here, we show that MAP3K4 controls the activity of the histone acetyltransferase CBP, and that acetylation of histone H2B by CBP is specifically required to maintain the epithelial phenotype. Combined loss of MAP3K4/CBP activity represses expression of epithelial genes and causes TS cells to undergo EMT while maintaining their self-renewal and multipotency properties. The expression profile of MAP3K4 deficient TS cells defines an H2B acetylation regulated gene signature that closely overlaps with that of human breast cancer cells. Taken together, our data define an epigenetic switch that maintains the epithelial phenotype in TS cells and reveal previously unrecognized genes potentially contributing to breast cancer.
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| Overall design |
Three separate trophoblast stem (TS) cell conditions were compared to define the gene expression changes that occur with the induction of epithelial-mesenchymal transition (EMT) in TS cells. These conditions were TS cells differentiated for 4 days (T^Diff), TS cells differentiated for 4-days and isolated following invasion through Matrigel (T^Inv), and TS cells with an inactive MAP3K4 (TS^KI4). All conditions were normalized to wild-type control TS cells (TS^WT). T^Diff and T^Inv were analyzed in triplicate. TS^KI4 was analyzed in duplicate in two independent biological replicates.
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| Contributor(s) |
Abell AN, Vincent Jordan NM, Huang W, Prat A, Midland AA, Johnson NL, Granger DA, Mieczkowski PA, Perou CM, Gomez SM, Li L, Johnson GL |
| Citation(s) |
21549327 |
| Submission date |
Mar 10, 2011 |
| Last update date |
May 10, 2018 |
| Contact name |
Gary Johnson |
| E-mail(s) |
glj@med.unc.edu
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| Organization name |
UNC-Chapel Hill
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| Department |
Pharmacology
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| Lab |
Johnson
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| Street address |
120 Mason Farm Drive,4009 Genetic Medicine Building,CB#7365
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| City |
Chapel Hill |
| State/province |
NC |
| ZIP/Postal code |
27599 |
| Country |
USA |
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| Platforms (1) |
| GPL4134 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Feature Number version) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA137993 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE27883_RAW.tar |
6.6 Mb |
(http)(custom) |
TAR |
| Processed data included within Sample table |
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