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Mus musculus

ABSTRACT: Essential and unexpected role of YY1 to promote mesodermal cardiac differentiation

PROVIDER: PRJNA152599 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR402770.fastq.gz	Fastqsanger.gz
	SRR402771.fastq.gz	Fastqsanger.gz
	SRR402772.fastq.gz	Fastqsanger.gz

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Essential and unexpected role of YY1 to promote mesodermal cardiac differentiation

Project description: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. 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.

2013-06-01 | E-GEOD-35370 | biostudies-arrayexpress

Essential and unexpected role of YY1 to promote mesodermal cardiac differentiation

2013-06-01 | GSE35370 | GEO

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Project description:YY1 plays an essential role at all stages of B cell differentiation [RNA-seq]

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Project description:YY1 plays an essential role at all stages of B cell differentiation [ChIP-seq]

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Project description:The aim was to assess the role of HAND1 in cardiac differentiation. The differentiation protocol was designed to promote cell diversity. For wild-type and HAND1-null cell lines we combined cells differentiating under different conditions: 50% control, 25% SB-treated (day 2-3) and 25% DMH1-treated (day 2-3). The addition of SB at day 2, inhibited SMAD2/3 phosphorylation and created a high BMP signalling bias to restrict cardiac differentiation in favour of other mesodermal lineages, whereas the addition of DMH1 at day 2, inhibited SMAD1/5/8 phosphorylation to create a high Activin signaling bias to promote the co-differentiation of endoderm. Samples were collected at days 3, 4, 5, 6, 7, 8 and 10 for wild-type and HAND1-null populations. An additional day 7 and 8 sample was included for the wild-type, which was generated in the same condition.

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