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Published on: October 28, 2011
REST-VP16 activates multiple neuronal differentiation genes in human NT2 cells
A Immaneni1, P Lawinger, Z Zhao
1University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Box 316, Houston, TX 77030, USA.
Nucleic Acids Research
|August 23, 2000
Summary
The recombinant REST-VP16 transcription factor activates neuronal genes. This tool aids in studying neuronal differentiation and related diseases.
Area of Science:
- Neuroscience
- Molecular Biology
- Gene Regulation
Background:
- The RE1-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) represses neuronal gene transcription in non-neuronal cells.
- REST/NRSF(-/-) mice indicate that repression alone is insufficient for neuronal gene expression; activators are also necessary.
Purpose of the Study:
- To construct a novel recombinant transcription factor, REST-VP16, by fusing REST/NRSF with the VP16 activation domain.
- To investigate the ability of REST-VP16 to activate neuronal gene expression in various cell types.
Main Methods:
- Construction of the REST-VP16 recombinant transcription factor.
- Transient transfection assays in mammalian cells.
- Adenoviral vector-mediated expression in NT2 cells (human committed neuronal progenitor cells).
Main Results:
- REST-VP16 activates plasmid-encoded neuronal promoters and endogenous REST/NRSF target genes via the RE1 binding site/neuron-restrictive enhancer element (RE1/NRSE).
- Activation occurs even without other required factors.
- Adenoviral expression of REST-VP16 in NT2 cells induces characteristic neuronal differentiation markers.
Conclusions:
- REST-VP16 functions as an activator, overcoming the need for additional factors in neuronal gene expression.
- REST-VP16 is a valuable tool for exploring neuronal differentiation pathways.
- This approach can advance the study of neuronal diseases linked to dysregulated differentiation.
