Searching across hundreds of databases
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 ~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.
Pubmed ID: 23326246 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
NIGMS places great emphasis on the support of individual, investigator-initiated grants within its scientific mission areas. Most grants are for research projects (R01), but NIGMS also funds program projects (P01) as well as some research resources. The Institute encourages research in certain scientific areas through requests for applications and program announcements. This website has information for upcoming grants, minority grants as well as training opportunities in medical research in the following disciplines: cell biology, biophysics, genetics, developmental biology, pharmacology, physiology, biological chemistry, bioinformatics, and computational biology.
View all literature mentionsA national institute that investigates human development throughout the entire life process, focusing on understanding developmental disabilities, including intellectual and developmental disabilities, and illuminating important events that occur during pregnancy. The NICHD conducts and supports laboratory research, clinical trials, and epidemiological studies that explore health processes; examines the impact of disabilities, diseases, and defects on the lives of individuals; and sponsors training programs for scientists, doctors, and researchers to ensure that NICHD research can continue. The Institute also supports research training across all its programs. In addition, an overarching responsibility of the NICHD is to disseminate information that emanates from Institute research programs to researchers, practitioners, other health care professionals, and the public.
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
