Chromatin remodeling pathways in smooth muscle cell differentiation, and evidence for an integral role for XXXX .

@entity1 @entity32 @entity455 @entity3493 @entity3996 @entity3960
BACKGROUND: Phenotypic alteration of vascular @entity3960 ( @entity3960 ) in response to @entity32 is an essential component of @entity455 . Evidence suggests that this process is dependent on epigenetic regulatory processes. @entity3493 , a histone acetyltransferase (HAT), activates crucial muscle-specific promoters in terminal (non- @entity3960 ) myocyte differentiation, and may be essential to @entity3960 modulation as well. RESULTS: We performed a subanalysis examining transcriptional time-course microarray data obtained using the A404 model of @entity3960 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, @entity3996 , a histone deacetylase inhibitor, accelerated expression of @entity3960 differentiation markers in this model. Ontology analysis indicated a high degree of @entity3493 involvement in @entity3960 differentiation, with 60.7% of the known @entity3493 interactome showing significant expression changes. Knockdown of @entity3493 expression accelerated @entity3960 differentiation in A404 cells and @entity1 SMCs, while inhibition of @entity3493 activity blunted @entity3960 differentiation. The results suggest a central but complex role for @entity3493 in @entity3960 phenotypic modulation. CONCLUSIONS: Our results support the hypothesis that chromatin remodeling is important for @entity3960 phenotypic switching, and detail wide-ranging involvement of several epigenetic modification families. Additionally, the transcriptional coactivator @entity3493 may be partially degraded during @entity3960 differentiation, leaving an activated subpopulation with increased HAT activity and @entity3960 differentiation-gene specificity.
