BRAHMA ATPase of the SWI/SNF Chromatin Remodeling Complex Acts as a Positive Regulator of Gibberellin-Mediated Responses in Arabidopsis

SWI/SNF chromatin remodeling complexes perform a pivotal function in the regulation of eukaryotic gene expression. Arabidopsis (Arabidopsis thaliana) mutants in major SWI/SNF subunits display embryo-lethal or dwarf phenotypes, indicating their critical role in molecular pathways controlling development and growth. As gibberellins (GA) are major positive regulators of plant growth, we wanted to establish whether there is a link between SWI/SNF and GA signaling in Arabidopsis. This study revealed that in brm-1 plants, depleted in SWI/SNF BRAHMA (BRM) ATPase, a number of GA-related phenotypic traits are GA-sensitive and that the loss of BRM results in markedly decreased level of endogenous bioactive GA. Transcriptional profiling of brm-1 and the GA biosynthesis mutant ga1-3, as well as the ga1-3/brm-1 double mutant demonstrated that BRM affects the expression of a large set of GA-responsive genes including genes responsible for GA biosynthesis and signaling. Furthermore, we found that BRM acts as an activator and directly associates with promoters of GA3ox1, a GA biosynthetic gene, and SCL3, implicated in positive regulation of the GA pathway. Many GA-responsive gene expression alterations in the brm-1 mutant are likely due to depleted levels of active GAs. However, the analysis of genetic interactions between BRM and the DELLA GA pathway repressors, revealed that BRM also acts on GA-responsive genes independently of its effect on GA level. Given the central position occupied by SWI/SNF complexes within regulatory networks controlling fundamental biological processes, the identification of diverse functional intersections of BRM with GA-dependent processes in this study suggests a role for SWI/SNF in facilitating crosstalk between GA-mediated regulation and other cellular pathways

Abstract 527: The Functional Significance of the Adenosine A _2b Receptor in the Internal Mammary Artery

Objective: The endothelium is the initial target that leads to cardiovascular disease. Knowing that the internal mammary arteries (IMA) are resistant to the development of atherosclerosis, which contrasts with coronary arteries (Cor) which are athero-prone, we hypothesize that genes over-expressed in the endothelial cells (ECs) of between these two arteries will identify genes that resist atherosclerosis. Methods and Results: Microarray analysis showed over 1,000 differentially expressed in the ECs of IMA vs Cor. The most statistically significant different gene was the adenosine A 2B receptor. This indicates the A 2B receptor may be involved in a resistance to atherosclerosis. Western blot analysis showed higher A 2B expression in the IMA than in coronary arteries with or without disease from proteins harvested from these human arteries and ECs. Overexpression of A 2B in ECs blunted: monocyte adhesion, cell adhesion molecule expression, migration, and the transendothelial migration of monocytes-- processes directly associated with the development of atherosclerosis. Knockdown of A 2B expression by siRNA promoted these processes. Conclusions: ECs derived from the IMA and Cor are distinctly different in gene expression, which may be responsible for their differential sensitivities for atherosclerosis. This study defined how the A 2B receptor may act as an atherosclerotic-resistance gene, which blunted monocyte adhesion and cell adhesion molecule expression, EC migration and retarded the transendothelial migration of monocytes. </jats:p