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Series GSE35370 Query DataSets for GSE35370
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
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.
 
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.
 
Contributor(s) Gregoire S, Wu S
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Jan 26, 2012
Last update date May 15, 2019
Contact name Serge Gregoire
Organization name Massachusetts General Hospital
Street address 185 Cambridge ST
City Boston
State/province MA
ZIP/Postal code 02114
Country USA
 
Platforms (1)
GPL9185 Illumina Genome Analyzer (Mus musculus)
Samples (3)
GSM866992 FACS-sorted eGFP+ CPCs, rep1
GSM866993 FACS-sorted eGFP+ CPCs, rep2
GSM866994 FACS-sorted eGFP+ CPCs input
Relations
SRA SRP010604
BioProject PRJNA152599

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Supplementary file Size Download File type/resource
GSE35370_RAW.tar 280.4 Mb (http)(custom) TAR (of BED, BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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