Antagonistic Effects of Grg6 and Groucho/TLE on the Transcription Repression Activity of Brain Factor 1/FoxG1 and Cortical Neuron Differentiation
| Autor: | Jinjun Dang, Cheryl D. Helgason, Brad G. Hoffman, Stephanie Belanger-Jasmin, Stefano Stifani, Zhifeng Dong, Harshila Patel, Nathalie Marcal |
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| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Transcription
Genetic Cellular differentiation Molecular Sequence Data Gene Expression Down-Regulation Nerve Tissue Proteins Biology Gene product Mice Forkhead Transcription Factors WD40 repeat Transcription (biology) Animals Humans Amino Acid Sequence Molecular Biology Transcription factor Cerebral Cortex Neurons Neurogenesis Gene Expression Regulation Developmental Cell Differentiation Cell Biology Molecular biology Neural stem cell Cell biology Repressor Proteins lipids (amino acids peptides and proteins) RNA Interference Co-Repressor Proteins |
| Popis: | Groucho (Gro)/TLE transcriptional corepressors are involved in a variety of developmental mechanisms, including neuronal differentiation. They contain a conserved C-terminal WD40 repeat domain that mediates interactions with several DNA-binding proteins. In particular, Gro/TLE1 interacts with forkhead transcription factor brain factor 1 (BF-1; also termed FoxG1). BF-1 is an essential regulator of neuronal differentiation during cerebral cortex development and represses transcription together with Gro/TLE1. Gro/TLE-related gene product 6 (Grg6) shares with Gro/TLEs a conserved WD40 repeat domain but is more distantly related at its N-terminal half. We demonstrate that Grg6 is expressed in cortical neural progenitor cells and interacts with BF-1. In contrast to Gro/TLE1, however, Grg6 does not promote, but rather suppresses, BF-1-mediated transcriptional repression. Consistent with these observations, Grg6 interferes with the binding of Gro/TLE1 to BF-1 and does not repress transcription when targeted to DNA. Moreover, coexpression of Grg6 and BF-1 in cortical progenitor cells leads to a decrease in the number of proliferating cells and increased neuronal differentiation. Conversely, Grg6 knockdown by RNA interference causes decreased neurogenesis. These results identify a new role for Grg6 in cortical neuron development and establish a functional link between Grg6 and BF-1. |
| Databáze: | OpenAIRE |
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