Chromatin Remodeling Factor Brg1 in Embryonic Development

Download or read book Chromatin Remodeling Factor Brg1 in Embryonic Development written by Chien-Jung Lin and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: During embryonic development, dynamic remodeling of the chromatin landscape is required for the transcriptional machinery to access the genomic DNA in a spatiotemporally controlled manner. This intricate level of regulation allows precise gene regulation, necessary for complex morphogenetic processes. The Brg1/Brm-associated factor (BAF) complex is a multisubunit, ATP-dependent chromatin remodeling complex. Among the subunits, Brg1 is an ATPase that is critical for the function of the complex. Here, we study the role of Brg1 in foregut and cardiac outflow tract development. In the foregut, Brg1 functions with HDAC proteins in the ventral epithelium to regulate Nkx2-1 expression, essential for foregut septation into trachea and esophagus. In the absence of Brg1, embryos develop a single-tube foregut, reminiscent of human patients with tracheoesophageal fistula. In the developing heart, Brg1 functions in the secondary heart field-derived myocardium to control Semaphorin 3c (Sema3c) expression, essential for the outflow tract to septate into pulmonary artery and aorta. Deletion of Brg1 in the secondary heart field results in decreased neural crest cell colonization of the outflow tract, leading to a phenotype similar to the persistent truncus arteriosus pathology. Brg1 cooperates with HDAC proteins and Chd7 in the outflow tract myocardium to control Sema3c expression. These studies demonstrate novel functions and molecular mechanisms of Brg1 in foregut and cardiovascular development.