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SATB2 interacts with chromatin-remodeling molecules in differentiating cortical neurons
- Source :
- The European journal of neuroscience. 27(4)
- Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- Immunoblotting
Histone Deacetylase 1
Biology
Chromatin remodeling
Histone Deacetylases
Rats, Mutant Strains
Epigenesis, Genetic
Rats, Sprague-Dawley
Histone H1
Histone H2A
Histone code
Animals
Cells, Cultured
Cerebral Cortex
Neurons
General Neuroscience
Cell Differentiation
Methionine Adenosyltransferase
ChIP-on-chip
Chromatin Assembly and Disassembly
Mi-2/NuRD complex
Molecular biology
Immunohistochemistry
Chromatin
Rats
DNA-Binding Proteins
Chromatin immunoprecipitation
Subjects
Details
- ISSN :
- 14609568
- Volume :
- 27
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- The European journal of neuroscience
- Accession number :
- edsair.doi.dedup.....f4cee5b755dd6dcd3dcc46194b8bb208