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

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.

SUBMITTER: Gregoire S

PROVIDER: S-EPMC3629954 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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

Gregoire Serge S Karra Ravi R Passer Derek D Deutsch Marcus-André MA Krane Markus M Feistritzer Rebecca R Sturzu Anthony A Domian Ibrahim I Saga Yumiko Y Wu Sean M SM

Circulation research 20130110 6

<h4>Rationale</h4>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).<h4>Objective</h4>To identify novel regulators of mesodermal cardiac lineage commitment.<h4>Methods and results</h4>We performed a bioinformatic-based transcription factor binding site analysis on upstream promoter regions of genes that are enriched in embryoni ...[more]

PMID: 23307821

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Project description:BackgroundYin Yang-1 (YY1) is identified as a transcription factor with multiple functions. However, the role of YY1 in tumorigenesis remains controversial and its regulatory effects may depend upon not only cancer types, but also its interacting partners, chromatin structure, and the context in which it acts. It has been detected that YY1 was highly expressed in colorectal cancer (CRC). Intriguingly, many YY1-repressed genes exhibit tumor suppressive potential while YY1 silencing is related to chemotherapy resistance. Therefore, it is crucial to meticulously explore YY1 protein structure and the dynamic alteration of its interactome in each cancer type. This review attempts to describe the structure of YY1, summarize the mechanism that influence the expression level of YY1 and also highlight the recent advances in our understanding of regulatory insights of YY1 functions in CRC.MethodsRelated studies were identified through scoping search of PubMed, Web of science, Scopus and Emhase concerning the terms of "colorectal cancer", colorectal carcinoma" or CRC with "YY1". The retrieval strategy included title, abstract, and keywords with no language limitations. All the included articles were categorized depending on the mechanisms they explored.ResultsIn total, 170 articles were identified for further screening. After removing the duplication, not relevant outcomes and review articles, 34 were finally included in the review. Among them, 10 articles revealed the reasons of YY1 high expression in CRC, 13 articles explored YY1 function in CRC, and 11 articles fell into both aspects. In addition, we also summarized 10 clinical trials concerning the expression and activity of YY1 in various diseases, which offers a hint for future application.ConclusionsYY1 is highly expressed in CRC and broadly recognized as an oncogenic factor during the whole course of CRC. Sporadic controversial views are raised in term of CRC treatment, reminding us that future studies should take the influence of therapeutic regimens into concern.

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

Publications

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

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