SATB1 dissociates from chromatin early during apoptosis.
(A) Confocal analysis of immunofluorescence staining of lamin B and
SATB1. Rat thymocytes treated with 2 μM dexamethasone for 2 h
were double immunostained with anti-SATB1 antibody (red) and anti-lamin
B antibody (green). Individual cells in very early (a), middle (b), and
late stages of apoptosis (c) are shown. (B) Double staining of genomic
DNA and SATB1 with Hoechst 33258 dye (top) and anti-SATB1 antibody
(bottom) from thymocytes treated with dexamethasone (dex) for 0, 1, and
2 h. Arrows indicate apoptotic cells with apparent morphological
alteration. Differences in SATB1 staining pattern and the sizes of
cells reflect the different developmental stages of the thymocyte (our
unpublished result). (C) (Top) Dissociation of SATB1 from chromatin
early in apoptosis. Dexamethasone-treated thymocytes at different time
points were incubated with 50 mM cis-DDP and solubilized
in 4% SDS, and DNA-protein complexes (cross-linked genomic DNA
fraction) were pelleted by ultracentrifugation. The pellets were
resuspended in 5 M urea–2% SDS, and untracentrifugation was repeated
to isolate DNA-cross-linked proteins. The pellets were sonicated and
treated with DNase I. The solubilized protein fractions were subjected
to SDS–7.5% PAGE and Western blot analysis using anti-SATB1
polyclonal serum. Positions of the molecular mass markers (in
kilodaltons) are indicated on the left. Arrow, band corresponding to
full-length SATB1. Other faint bands, representing nonspecific
cross-reactivity of the anti-SATB1 antibody, became visible only after
longer exposure of a Western blot. (Bottom) Densitometric analysis of
the SATB1 signals shown at the top. Intensity of the band corresponding
to full-length SATB1 was quantitated using a laser densitometer and
plotted as a function of time after dexamethasone treatment. All values
were normalized to the intensity of the SATB1 signal in the absence of
dexamethasone treatment (lane 2) and were expressed as percentages of
the zero time value.