Genome-Wide Screens for In Vivo Tinman Binding Sites Identify Cardiac Enhancers with Diverse Functional Architectures

Beitrag in einer Fachzeitschrift
(Originalarbeit)


Details zur Publikation

Autorinnen und Autoren: Jin H, Stojnic R, Adryan B, Ozdemir A, Stathopoulos A, Frasch M
Zeitschrift: PLoS Genetics
Verlag: PUBLIC LIBRARY SCIENCE
Jahr der Veröffentlichung: 2013
Band: 9
Heftnummer: 1
ISSN: 1553-7390
eISSN: 1553-7404


Abstract


The NK homeodomain factor Tinman is a crucial regulator of early mesoderm patterning and, together with the GATA factor Pannier and the Dorsocross T-box factors, serves as one of the key cardiogenic factors during specification and differentiation of heart cells. Although the basic framework of regulatory interactions driving heart development has been worked out, only about a dozen genes involved in heart development have been designated as direct Tinman target genes to date, and detailed information about the functional architectures of their cardiac enhancers is lacking. We have used immunoprecipitation of chromatin (ChIP) from embryos at two different stages of early cardiogenesis to obtain a global overview of the sequences bound by Tinman in vivo and their linked genes. Our data from the analysis of similar to 50 sequences with high Tinman occupancy show that the majority of such sequences act as enhancers in various mesodermal tissues in which Tinman is active. All of the dorsal mesodermal and cardiac enhancers, but not some of the others, require tinman function. The cardiac enhancers feature diverse arrangements of binding motifs for Tinman, Pannier, and Dorsocross. By employing these cardiac and non-cardiac enhancers in machine learning approaches, we identify a novel motif, termed CEE, as a classifier for cardiac enhancers. In vivo assays for the requirement of the binding motifs of Tinman, Pannier, and Dorsocross, as well as the CEE motifs in a set of cardiac enhancers, show that the Tinman sites are essential in all but one of the tested enhancers; although on occasion they can be functionally redundant with Dorsocross sites. The enhancers differ widely with respect to their requirement for Pannier, Dorsocross, and CEE sites, which we ascribe to their different position in the regulatory circuitry, their distinct temporal and spatial activities during cardiogenesis, and functional redundancies among different factor binding sites.



FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Frasch, Manfred Prof. Dr.
Lehrstuhl für Entwicklungsbiologie
Jin, Hong
Lehrstuhl für Entwicklungsbiologie


Einrichtungen weiterer Autorinnen und Autoren

California Institute of Technology (Caltech)
University of Cambridge


Zitierweisen

APA:
Jin, H., Stojnic, R., Adryan, B., Ozdemir, A., Stathopoulos, A., & Frasch, M. (2013). Genome-Wide Screens for In Vivo Tinman Binding Sites Identify Cardiac Enhancers with Diverse Functional Architectures. PLoS Genetics, 9(1). https://dx.doi.org/10.1371/journal.pgen.1003195

MLA:
Jin, Hong, et al. "Genome-Wide Screens for In Vivo Tinman Binding Sites Identify Cardiac Enhancers with Diverse Functional Architectures." PLoS Genetics 9.1 (2013).

BibTeX: 

Zuletzt aktualisiert 2019-03-06 um 10:53