Theoretical models suggest that gene silencing at the nuclear periphery may 
involve "closing" of chromatin by transcriptional repressors, such as histone 
deacetylases (HDACs). Here we provide experimental evidence confirming these 
predictions. Histone acetylation, chromatin compactness, and gene repression in 
lamina-interacting multigenic chromatin domains were analyzed in Drosophila S2 
cells in which B-type lamin, diverse HDACs, and lamina-associated proteins were 
downregulated by dsRNA. Lamin depletion resulted in decreased compactness of the 
repressed multigenic domain associated with its detachment from the lamina and 
enhanced histone acetylation. Our data reveal the major role for HDAC1 in 
mediating deacetylation, chromatin compaction, and gene silencing in the 
multigenic domain, and an auxiliary role for HDAC3 that is required for 
retention of the domain at the lamina. These findings demonstrate the manifold 
and central involvement of class I HDACs in regulation of lamina-associated 
genes, illuminating a mechanism by which these enzymes can orchestrate normal 
and pathological development.