Neuronal depolarization leads to a reduction of CtBP1/YY1 interaction
in vitro and triggers CtBP1 dissociation from the proximal
Mmp-9 promoter in vivo in the cell nuclei of the rat
hippocampus. A, CtBP1 is expressed in cell nuclei of the rat
hippocampal cells and up-regulated after PTZ-induced seizures. Equal amounts
(20 μg) of nuclear cell lysates obtained from the unstimulated
(-PTZ) as well as from the PTZ-stimulated (2 h; +PTZ) rat
hippocampi were analyzed by Western blot with anti-CtBP1 antibody. As a
loading control, results of Western blot analysis for histone H3 are shown.
B, CtBP1 physically interacts with YY1 in a depolarization-dependent
manner in cell nuclei of the rat hippocampus. Equal amounts (300 μg) of
nuclear cell lysates obtained from the unstimulated (-PTZ) as well as
from the PTZ-stimulated (2 h; +PTZ) rat hippocampi were
immunoprecipitated (IPα) with anti-CtBP1 or control (isotype)
antibody and analyzed for YY1 expression by Western blot. As a positive
control, protein nuclear cell lysate obtained from the unstimulated hippocampi
has been used (resolved in the input lane). Unmodified YY1
(YY1) and its ubiquitinated form (uYY1) are indicated.
C, interaction of CtBP1 with ubiquitinated YY1 is neuronal
activity-dependent in cell nuclei of the rat hippocampus. Equal amounts (300
μg) of nuclear cell lysates obtained from the unstimulated (-PTZ)
as well as from the PTZ-stimulated (2 h; +PTZ) rat hippocampi were
immunoprecipitated with anti-CtBP1 or control (isotype) antibody and analyzed
for ubiquitin expression by Western blot. The ubiquitinated YY1
(uYY1) is indicated. D, CtBP1 occupies the proximal
Mmp-9 promoter in the unstimulated hippocampus and is released after
PTZ-evoked neuronal depolarization. Evaluation by real time PCR of the
proximal Mmp-9 promoter content in DNA samples obtained because of
immunoprecipitation of chromatin bound to CtBP1 from the unstimulated
(-PTZ) as well as from the PTZ-stimulated (2 h; +PTZ) rat
hippocampi. Control ChIP reactions were performed with isotype antibody.
Error bars represent the mean ± S.D. (n = 3;
*, p < 0.05; **, p < 0.01).