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A, T47D cells depleted of HDAC2, but not of HDAC1, showed increased DNA sensitivity to nuclease digestion by the ISNT DNA hypersensitivity assay. Cells transfected with nonsilencing siRNA followed by incubation with 2 mmol/L VPAfor 48 h served as a positive control. B, electron micrographs of cells transfected with nonsilencing siRNA or depleted of HDAC1 or HDAC2. Arrows, dense areas of heterochromatin clusters. C, stacked bar graph depicting the mean heterochromatin content (shaded) per cell per transfection condition. Heterochromatin content was determined by point-count intercept morphometry analysis of the electron micrographs for 50 cells per transfection condition. Statistical analysis by Student’s t test indicated a significant (P < 0.0001) reduction in the heterochromatin content in cells depleted of HDAC2 but not of HDAC1 compared with cells transfected with nonsilencing siRNA. For details, see Marchion et al., in this issue.