SWI/SNF Chromatin-remodeling enzymes Brahma-related Gene 1(BRG1) and Brahma (BRM) are dispensable in multiple models of postnatal angiogenesis but are required for vascular integrity in infant mice

Background--mammalian switch/sucrose nonfermentable (swi/snf) adenosine triphosphate (atp)-dependent chromatinremodeling complexes play important roles in embryonic vascular development by modulating transcription of specific target genes. we sought to determine whether swi/snf complexes likewise impact postnatal physiological and pathological angiogenesis.methods and results--brahma-related gene 1 (brg1) and brahma gene (brm) are atpases within mammalian swi/snf complexes and are essential for the complexes to function. using mice with vascular-specific mutations in brg1 or with a global mutation in brm,we employed 3 models to test the role of these atpases in postnatal angiogenesis. we analyzed neonatal retinal angiogenesis,exercise-induced angiogenesis in adult quadriceps muscles,and tumor angiogenesis in control and mutant animals.we found no evidence of defective angiogenesis in brg1 or brm mutants using these 3 models. brg1/brm double mutants likewise show no evidence of vascular defects in the neonatal retina or tumor angiogenesis models. however,100% of brg1/brm-double mutants in which brg1 deletion is induced at postnatal day 3 (p3) die by p19 with hemorrhaging in the small intestine and heart. conclusions--despite their important roles in embryonic vascular development,swi/snf chromatin-remodeling complexes display a surprising lack of participation in the 3 models of postnatal angiogenesis we analyzed. however,these complexes are essential for maintaining vascular integrity in specific tissue beds before weaning. these findings highlight the temporal and spatial specificity of swi/snf activities in the vasculature and may indicate that other chromatin-remodeling complexes play redundant or more essential roles during physiological and pathological postnatal vascular development. 2015 the authors. published on behalf of the american heart association,inc.