| Autor: |
Branigan GL; Medical Scientist Training Program, Center for Innovation in Brain Science, Department of Pharmacology, University of Arizona College of Medicine-Tucson, 1501 N Campbell Ave., Tucson, AZ 85724, USA., Olsen KS; Biological and Biomedical Sciences Program, Department of Microbiology and Immunology, University of North Carolina School of Medicine-Chapel Hill, 321 S Columbia St., Chapel Hill, NC 27516, USA., Burda I; Department of Molecular Biology and Genetics, Weill Institute for Cell & Molecular Biology, Cornell University, 239 Weill Hall, Ithaca, NY 14853, USA., Haemmerle MW; Institute for Diabetes, Obesity, and Metabolism, Smilow Center for Translational Research, Perelman School of Medicine, University of Pennsylvania, Room 12-124, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA., Ho J; Robert Wood Johnson Medical School, Rutgers University, Clinical Academic Building (CAB), 125 Paterson St., New Brunswick, NJ 08901, USA., Venuto A; Department of Biology, East Carolina University, Greenville, NC 27858, USA., D'Antonio ND; Sidney Kimmel Medical College, Thomas Jefferson University Hospital, 1025 Walnut St. #100, Philadelphia, PA 19107, USA., Briggs IE; Department of Biology, Villanova University, 800 Lancaster Ave., Villanova, PA 19085, USA., DiBenedetto AJ; Department of Biology, Villanova University, 800 Lancaster Ave., Villanova, PA 19085, USA. |
| Abstrakt: |
Brd2 belongs to the BET family of epigenetic transcriptional co-regulators that act as adaptor-scaffolds for the assembly of chromatin-modifying complexes and other factors at target gene promoters. Brd2 is a protooncogene and candidate gene for juvenile myoclonic epilepsy in humans, a homeobox gene regulator in Drosophila, and a maternal-zygotic factor and cell death modulator that is necessary for normal development of the vertebrate central nervous system (CNS). As two copies of Brd2 exist in zebrafish, we use antisense morpholino knockdown to probe the role of paralog Brd2b, as a comparative study to Brd2a, the ortholog of human Brd2. A deficiency in either paralog results in excess cell death and dysmorphology of the CNS, whereas only Brd2b deficiency leads to loss of circulation and occlusion of the pronephric duct. Co-knockdown of both paralogs suppresses single morphant defects, while co-injection of morpholinos with paralogous RNA enhances them, suggesting novel genetic interaction with functional antagonism. Brd2 diversification includes paralog-specific RNA variants, a distinct localization of maternal factors, and shared and unique spatiotemporal expression, providing unique insight into the evolution and potential functions of this gene. |
