SATB2 interacts with chromatin‐remodeling molecules in differentiating cortical neurons

During our search for developmental regulators of neuronal differentiation, we identified special AT‐rich sequence‐binding protein (SATB)2 that is specifically expressed in the developing rat neocortex and binds to AT‐rich DNA elements. Here we investigated whether the regulatory function of SATB2 involves chromatin remodeling at the AT‐rich DNA site. In‐vitro and in‐vivo assays using a DNA affinity pre‐incubation specificity test of recognition and chromatin immunoprecipitation showed that SATB2 specifically binds to histone deacetylase 1 and metastasis‐associated protein 2, members of the nucleosome‐remodeling and histone deacetylase complex. Double immunohistochemistry showed that, in the developing rat neocortex, SATB2 is coexpressed with both proteins. Using a cell culture model, we showed that trichostatin A treatment, which blocks the activities of histone deacetylases, reverses the AT‐rich dsDNA‐dependent repressor effect of SATB2. These findings suggested that the molecular regulatory function of SATB2 involves modification of the chromatin structure. Semi‐quantitative chromatin immunoprecipitation analysis of cortices from SATB2 mutant and wild‐type animals indicated that, in the knock‐out brains, SATB2 is replaced in the chromatin‐remodeling complex by AU‐rich element RNA binding protein 1, another AT‐rich DNA binding protein also expressed in differentiating cortical neurons. These results suggested that an altered chromatin structure, due to the presence of different AT‐rich DNA binding proteins in the chromatin‐remodeling complex, may contribute to the developmental abnormalities observed in the SATB2 mutant animals. These findings also raised the interesting possibility that SATB2, along with other AT‐rich DNA binding proteins, is involved in mediating epigenetic influences during cortical development.

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