1. RE1 Silencing Transcription Factor Maintains a Repressive Chromatin Environment in Embryonic Hippocampal Neural Stem Cells
- Author
-
Miyoko Street, Deborah J. Greenway, Aaron R. Jeffries, and Noel J. Buckley
- Subjects
Chromatin Immunoprecipitation ,Cellular differentiation ,Nerve Tissue Proteins ,Transcription coregulator ,RE1-silencing transcription factor ,Regulatory Sequences, Nucleic Acid ,Biology ,Hippocampus ,Histone Deacetylases ,Histones ,Mice ,Tubulin ,Animals ,Humans ,Gene Silencing ,RNA, Messenger ,Epigenetics ,Embryonic Stem Cells ,Neurons ,Regulation of gene expression ,Genetics ,Cell Differentiation ,Cell Biology ,Embryonic stem cell ,Chromatin ,Neural stem cell ,Cell biology ,DNA-Binding Proteins ,Repressor Proteins ,Protein Transport ,Sin3 Histone Deacetylase and Corepressor Complex ,biology.protein ,Molecular Medicine ,Cattle ,Co-Repressor Proteins ,Protein Binding ,Transcription Factors ,Developmental Biology - Abstract
The control of gene expression in neural stem cells is key to understanding their developmental and therapeutic potential, yet we know little of the transcriptional mechanisms that underlie their differentiation. Recent evidence has implicated the RE1 silencing transcription factor (REST) in neuronal differentiation. However, the means by which REST regulates transcription in neural stem cells remain unclear. Here, we show that REST recruits distinct corepressor platforms in neural stem cells. REST is able to both silence and repress neuronal genes in embryonic hippocampal neural stem cells by creating a chromatin environment that contains both repressive local epigenetic signature (characterized by low levels of histones H4 and H3K9 acetylation and elevated dimethylation of H3K9) and H3K4 methylation, which are characteristic of gene activation. Furthermore, inhibition of REST function leads to activation of several neuron-specific genes but does not lead to overt formation of mature neurons, supporting the notion that REST regulates part, but not all, of the neuronal differentiation program. more...
- Published
- 2006
- Full Text
- View/download PDF