title: Cardiac genes show contextual SWI/SNF interactions with distinguishable gene activities.
abstract: Recent experimental evidence indicates that cardiac and chromatin remodeling are associated with changes in gene expression mediated by Brahma-related gene 1 (Brg1), a member of the large group of SWI/SNF subunits. The second catalytic member of this family is Brahma (Brm), which shares close sequence homology to Brg1. Despite the sequence similarities, these determinants are found in distinct regulatory complexes; however, the precise nature and role of these remodeling enzymes in the failing heart remains unknown. Here we have hypothesized that Brg1 and Brm form distinct complexes in regulating gene expression in an animal model of cardiac hypertrophy. We have identified that the hypertrophic myocardium is characterized by profound morphological changes associated with increased expression of ANP (Nppa), BNP (Nppb) and β-MHC (Myh7) genes, correlating with reduced expression of the α-MHC (Myh6) and SERCA2A (Atp2a2) genes. Histone deacetylase inhibition prevented left ventricular hypertrophy indicating that the re-expression of gene activity can be associated with both contextual and distinct SWI/SNF interactions. We hypothesize that cardiac hypertrophy and the fetal gene expression program are associated with distinguishable binding of Brm and Brg1 on genes present in distinct complexes, suggesting possible independent-regulatory roles.
authors.affiliation: Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia.
authors.forename: Lisa
authors.initials: L
authors.lastname: Chang
authors.forename: Helen
authors.initials: H
authors.lastname: Kiriazis
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Gao
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Du
authors.forename: Assam
authors.initials: A
authors.lastname: El-Osta
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D009687:Nuclear Proteins; C499503:Smarca2 protein, mouse; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D004265:DNA Helicases; C506947:Atp2a2 protein, mouse