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Essential and unexpected role of Yin Yang 1 to promote mesodermal cardiac differentiation.

Publication ,  Journal Article
Gregoire, S; Karra, R; Passer, D; Deutsch, M-A; Krane, M; Feistritzer, R; Sturzu, A; Domian, I; Saga, Y; Wu, SM
Published in: Circ Res
March 15, 2013

RATIONALE: Cardiogenesis is regulated by a complex interplay between transcription factors. 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 embryonic stem cell-derived CPCs. From 32 candidate transcription factors screened, we found that Yin Yang 1 (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, in vivo chromatin immunoprecipitation, 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 embryonic stem cell-based assays in which we showed that the overexpression of YY1 enhanced the cardiogenic differentiation of embryonic stem cells into CPCs. CONCLUSIONS: 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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Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

March 15, 2013

Volume

112

Issue

6

Start / End Page

900 / 910

Location

United States

Related Subject Headings

  • YY1 Transcription Factor
  • Transcriptional Activation
  • Transcription Factors
  • Myoblasts, Cardiac
  • Mice
  • Homeodomain Proteins
  • Homeobox Protein Nkx-2.5
  • Genome-Wide Association Study
  • GATA4 Transcription Factor
  • Embryonic Stem Cells
 

Citation

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Gregoire, S., Karra, R., Passer, D., Deutsch, M.-A., Krane, M., Feistritzer, R., … Wu, S. M. (2013). Essential and unexpected role of Yin Yang 1 to promote mesodermal cardiac differentiation. Circ Res, 112(6), 900–910. https://doi.org/10.1161/CIRCRESAHA.113.259259
Gregoire, Serge, Ravi Karra, Derek Passer, Marcus-André Deutsch, Markus Krane, Rebecca Feistritzer, Anthony Sturzu, Ibrahim Domian, Yumiko Saga, and Sean M. Wu. “Essential and unexpected role of Yin Yang 1 to promote mesodermal cardiac differentiation.Circ Res 112, no. 6 (March 15, 2013): 900–910. https://doi.org/10.1161/CIRCRESAHA.113.259259.
Gregoire S, Karra R, Passer D, Deutsch M-A, Krane M, Feistritzer R, et al. Essential and unexpected role of Yin Yang 1 to promote mesodermal cardiac differentiation. Circ Res. 2013 Mar 15;112(6):900–10.
Gregoire, Serge, et al. “Essential and unexpected role of Yin Yang 1 to promote mesodermal cardiac differentiation.Circ Res, vol. 112, no. 6, Mar. 2013, pp. 900–10. Pubmed, doi:10.1161/CIRCRESAHA.113.259259.
Gregoire S, Karra R, Passer D, Deutsch M-A, Krane M, Feistritzer R, Sturzu A, Domian I, Saga Y, Wu SM. Essential and unexpected role of Yin Yang 1 to promote mesodermal cardiac differentiation. Circ Res. 2013 Mar 15;112(6):900–910.

Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

March 15, 2013

Volume

112

Issue

6

Start / End Page

900 / 910

Location

United States

Related Subject Headings

  • YY1 Transcription Factor
  • Transcriptional Activation
  • Transcription Factors
  • Myoblasts, Cardiac
  • Mice
  • Homeodomain Proteins
  • Homeobox Protein Nkx-2.5
  • Genome-Wide Association Study
  • GATA4 Transcription Factor
  • Embryonic Stem Cells