Chromatin Remodeling Pathways in Smooth Muscle Cell Differentiation, and Evidence for an Integral Role for p300

Phenotypic alteration of vascular smooth muscle cells (SMC) in response to injury or inflammation is an essential component of vascular disease. Evidence suggests that this process is dependent on epigenetic regulatory processes. P300, a histone acetyltransferase (HAT), activates crucial muscle-specific promoters in terminal (non-SMC) myocyte differentiation, and may be essential to SMC modulation as well.We performed a subanalysis examining transcriptional time-course microarray data obtained using the A404 model of SMC differentiation. Numerous chromatin remodeling genes (up to 62% of such genes on our array platform) showed significant regulation during differentiation. Members of several chromatin-remodeling families demonstrated involvement, including factors instrumental in histone modification, chromatin assembly-disassembly and DNA silencing, suggesting complex, multi-level systemic epigenetic regulation. Further, trichostatin A, a histone deacetylase inhibitor, accelerated expression of SMC differentiation markers in this model. Ontology analysis indicated a high degree of p300 involvement in SMC differentiation, with 60.7% of the known p300 interactome showing significant expression changes. Knockdown of p300 expression accelerated SMC differentiation in A404 cells and human SMCs, while inhibition of p300 HAT activity blunted SMC differentiation. The results suggest a central but complex role for p300 in SMC phenotypic modulation.Our results support the hypothesis that chromatin remodeling is important for SMC phenotypic switching, and detail wide-ranging involvement of several epigenetic modification families. Additionally, the transcriptional coactivator p300 may be partially degraded during SMC differentiation, leaving an activated subpopulation with increased HAT activity and SMC differentiation-gene specificity

Growth, proline accumulation and peroxidase activity in maize seedlings under osmotic stress

The influence of osmotic stress induced by polyethylene glycol (PEG) on plant growth, proline content and activities of soluble peroxidases was studied on 12 maize inbred lines at seedling stage. Reduction of plant growth, fresh weight and length of roots and shoots occurred in all of the studied genotypes and was followed by increase in free proline content of shoots and especially in roots of the majority of genotypes. Correlation analysis of changes in root proline content with growth parameters revealed direct positive correlation. Changes in root peroxidase activities ranged from approximately 40 % reduction to 20 % stimulation, depending on the genotype. It was shown that genotypes with higher proline changes under drought treatment exhibited lower peroxidase activities. In addition, genotypes with less pronounced root growth reduction under stress conditions exhibited increased peroxidase activities, as well as lower proline content. In the field experiments, grain yield was positively correlated with root proline content and negatively with root length changes in drought-treated seedlings grown in laboratory conditions