| 摘要 |
The molecular mechanisms by which central nervous system-specific genes are expressed only in the nervous system and repressed in other tissues remain a central issue in developmental and regulatory biology. The presently described invention outlines a dual mechanism of transcriptional downregulation in which the transcription factor REST/NRSF is a central component. The invention delineates short-term REST/NRSF-dependent active repression of neural-specific genes through the recruitment of histone deacetylases as well as long-term gene silencing through the recruitment of a novel biochemical complex which requires CpG methylation. Long-term silencing of neuronal-specific genes requires the recruitment of an associated corepressor, CoREST, that serves as a functional molecular beacon for the recruitment of molecular machinery that imposes silencing across a chromosomal interval, including transcriptional units that do not themselves contain REST/NRSF response elements.
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