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Published on: January 12, 2015
SATB2 interacts with chromatin-remodeling molecules in differentiating cortical neurons
Andrea B Gyorgy1, Marianna Szemes, Camino de Juan Romero
1Department of Anatomy, Physiology and Genetics, School of Medicine USU, Bethesda, MD 20814, USA.
The European Journal of Neuroscience
|March 13, 2008
Summary
Special AT-rich sequence-binding protein 2 (SATB2) regulates neuronal differentiation by remodeling chromatin structure. Its absence in mutant animals leads to developmental abnormalities, suggesting SATB2
Area of Science:
- Neuroscience
- Molecular Biology
- Epigenetics
Background:
- Neuronal differentiation requires precise regulation of gene expression.
- Special AT-rich sequence-binding protein 2 (SATB2) is a DNA-binding protein expressed in the developing neocortex.
- The role of SATB2 in chromatin remodeling during cortical development was investigated.
Purpose of the Study:
- To determine if SATB2's regulatory function involves chromatin remodeling.
- To investigate the interaction of SATB2 with chromatin remodeling complexes.
- To understand the impact of SATB2 on cortical development and epigenetic regulation.
Main Methods:
- In vitro and in vivo DNA affinity assays.
- Chromatin immunoprecipitation (ChIP) assays.
- Double immunohistochemistry and cell culture models.
- Analysis of SATB2 mutant and wild-type animal cortices.
Main Results:
- SATB2 specifically binds to histone deacetylase 1 and metastasis-associated protein 2 within the nucleosome-remodeling and histone deacetylase complex.
- SATB2 coexpression with these proteins was observed in the developing rat neocortex.
- Trichostatin A treatment reversed SATB2's repressor effect, indicating chromatin modification.
- In SATB2 knock-out brains, AU-rich element RNA binding protein 1 replaced SATB2 in the chromatin-remodeling complex.
- Altered chromatin structure in SATB2 mutants correlates with developmental abnormalities.
Conclusions:
- SATB2's molecular regulatory function involves chromatin structure modification.
- SATB2 plays a role in epigenetic influences during cortical development.
- Dysregulation of SATB2 and its associated chromatin remodeling complex contributes to cortical developmental abnormalities.
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