PMID- 16314515 OWN - NLM STAT- MEDLINE DCOM- 20060126 LR - 20181113 IS - 0270-7306 (Print) IS - 1098-5549 (Electronic) IS - 0270-7306 (Linking) VI - 25 IP - 24 DP - 2005 Dec TI - Antagonistic effects of Grg6 and Groucho/TLE on the transcription repression activity of brain factor 1/FoxG1 and cortical neuron differentiation. PG - 10916-29 AB - 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. FAU - Marcal, Nathalie AU - Marcal N AD - Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada. FAU - Patel, Harshila AU - Patel H FAU - Dong, Zhifeng AU - Dong Z FAU - Belanger-Jasmin, Stephanie AU - Belanger-Jasmin S FAU - Hoffman, Brad AU - Hoffman B FAU - Helgason, Cheryl D AU - Helgason CD FAU - Dang, Jinjun AU - Dang J FAU - Stifani, Stefano AU - Stifani S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (Co-Repressor Proteins) RN - 0 (Forkhead Transcription Factors) RN - 0 (Foxg1 protein, mouse) RN - 0 (Nerve Tissue Proteins) RN - 0 (Repressor Proteins) RN - 0 (Tle1 protein, mouse) RN - 0 (Tle6 protein, mouse) SB - IM MH - Amino Acid Sequence MH - Animals MH - Cell Differentiation/genetics MH - Cerebral Cortex/*cytology MH - Co-Repressor Proteins MH - Down-Regulation MH - Forkhead Transcription Factors/*antagonists & inhibitors MH - Gene Expression Regulation, Developmental MH - Humans MH - Mice MH - Molecular Sequence Data MH - Nerve Tissue Proteins/*antagonists & inhibitors MH - Neurons/*cytology/metabolism MH - RNA Interference MH - Repressor Proteins/genetics/*metabolism MH - Transcription, Genetic PMC - PMC1316978 EDAT- 2005/11/30 09:00 MHDA- 2006/01/27 09:00 PMCR- 2006/04/01 CRDT- 2005/11/30 09:00 PHST- 2005/11/30 09:00 [pubmed] PHST- 2006/01/27 09:00 [medline] PHST- 2005/11/30 09:00 [entrez] PHST- 2006/04/01 00:00 [pmc-release] AID - 25/24/10916 [pii] AID - 1535-05 [pii] AID - 10.1128/MCB.25.24.10916-10929.2005 [doi] PST - ppublish SO - Mol Cell Biol. 2005 Dec;25(24):10916-29. doi: 10.1128/MCB.25.24.10916-10929.2005.