Essential and unexpected role of Yin Yang 1 to promote mesodermal cardiac differentiation
Authors: Rebecca Feistritzer
Yumiko Saga
Sean M Wu
Markus Krane
Serge Gregoire
Derek Passer
Ibrahim Domian
Ravi Karra
Anthony Sturzu
Marcus-André Deutsch
Journal: Circulation research (2013)
Discipline: CLINICAL MEDICINE
Keywords: Cardiogenesis; Transcription factors; Mesodermal precursors; Cardiac progenitor cells; Yin Yang 1 (YY1)
Affiliations: Department of Medicine, Division of Cardiology, Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA (, Department of Medicine, Division of Cardiology, Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA (S.G., D.P., M.-A.D., M.K., R.F., A.S., I.D., S.M.W.); Department of Medicine, Division of Cardiology, Duke University Medical Center, Durham, NC (R.K.); Department of Cardiovascular Surgery, German Heart Center, Clinic at the Technische Universitaet Muenchen, Munich, Germany (M.-A.D., M.K.); Division of Mammalian Development, National Institute of Genetics, Mishima, Japan (Y.S....

Abstract:  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. 

Retracted: No

PubPeer comments:
 Figure 5A. Much more similar than you would expect. ![https: imgur.com z8r6RnQ.jpg ] , 
 Figure 5C. Much more similar than you would expect. ![https: imgur.com X4zddM7.jpg ] , 
 Figure 4D. Much more similar than you would expect. https: imgur.com gsniqxj , 
 #2 Figure 5C continued. CDC25A and Cyclin D1 panels. Much more similar than you would expect. https: imgur.com 0oPW8kb , 
 The Winship Cancer Institute of Emory University was supported by National Institutes of Health Grant P30CA138292 , 
 1st May 2020 retraction. https: www.jbc.org content 295 18 6250 VOLUME 292 (2017) PAGES 3531u20133540 This article has been withdrawn by Shuofeng Hu, Xiaomin Ying, Xiangming Zhang, and Ya Wang. Baocheng Hu, Xiang Wang, Ping Wang, Jian Wang, and Hongyan Wang could not be reached. In Fig. 1C, the DAPI and merged images for the no IR control were switched. The DNA-PKcs and actin immunoblots on the left appear to have been spliced. In Fig. 4C, the DNA-PKcs immunoblot appears to have been spliced. In Fig. 4D, lanes 1 and 5; lanes 2, 6, and 8; and lanes 3 and 7 of the DNA-PKcs immunoblot are the same. In the p-DNA-PKcs immunoblot, lanes 1 and 8, lanes 2 and 6, and lanes 3 and 7 are the same. In the CRY2 immunoblot, lanes 5 and 7 are the same. In the CDC25A immunoblot, lanes 3 and 8 are the same. In the GSK3B immunoblot, lanes 1 and 5 and lanes 3 and 7 are the same. Also in the GSK3B immunoblot, the upper GSK3B bands in lanes 6 and 8 are the same. Lanes 4 and 8 of the cyclin D1 immunoblot are the same. In Fig. 5A, the CDC25A immunoblot appears to have been spliced. Also in Fig. 5A, lanes 2u20134 and lanes 6u20138 of the CDC25A immunoblot are the same. Lanes 4u20136 and 7u20139 of the actin immunoblot are the same. In Fig. 5C, lane 1 of the CDC25A immunoblot was reused in lane 5, and lanes 3 and 4 were reused in lanes 7 and 8. In the GSK3B immunoblot, lanes 2u20134 and lanes 6u20138 are the same. Lane 1 of the cyclin D1 immunoblot was reused in lane 5, and lanes 3 and 4 were reused in lanes 7 and 8. Lanes 2u20134 of the actin immunoblot were reused in lanes 6u20138. ,