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| Status |
Public on Jun 01, 2013 |
| Title |
Essential and unexpected role of YY1 to promote mesodermal cardiac differentiation |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Rationale: Cardiogenesis is regulated by a complex interplay between transcription factors and chromatin-modifying enzymes. However, little is known about how these interactions regulate the transition from mesodermal precursors to cardiac progenitor cells (CPCs).
Objective: To identify novel regulators of mesodermal cardiac lineage commitment.
Methods and Results: We performed a bioinformatic-based transcription factor-binding site analysis on upstream promoter regions of genes that are enriched in ES cell-derived CPCs. From 32 candidate transcription factors screened, we found that YY1, a repressor of sarcomeric gene expression, is present in CPCs in vivo. Interestingly, we uncovered the ability of YY1 to transcriptionally activate Nkx2.5, a key marker of early cardiogenic commitment. YY1 regulates Nkx2.5 expression via a 2.1 kb cardiac-specific enhancer as demonstrated by in vitro luciferase-based assays and in vivo chromatin immunoprecipitation (ChIP) and genome-wide sequencing analysis. Furthermore, the ability of YY1 to activate Nkx2.5 expression depends on its cooperative interaction with GATA4 at a nearby chromatin. Cardiac mesoderm-specific loss-of-function of YY1 resulted in early embryonic lethality. This was corroborated in vitro by ES cell-based assays where we show that the over-expression of YY1 enhanced the cardiogenic differentiation ES cells into CPCs in a cell autonomous manner.
Conclusion: These results demonstrate an essential and unexpected role for YY1 to promote cardiogenesis as a transcriptional activator of Nkx2.5 and other CPC-enriched genes.
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| Overall design |
We report the identification of putative YY1 target genes in cardiac progenitor cells (CPCs). Two samples of independently FACS-purified eGFP+ CPCs were examined against the input.
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| Contributor(s) |
Gregoire S, Wu S |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Jan 26, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Serge Gregoire |
| Organization name |
Massachusetts General Hospital
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| Street address |
185 Cambridge ST
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02114 |
| Country |
USA |
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| Platforms (1) |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
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| Samples (3) |
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| Relations |
| SRA |
SRP010604 |
| BioProject |
PRJNA152599 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE35370_RAW.tar |
280.4 Mb |
(http)(custom) |
TAR (of BED, BIGWIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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