The sequential steps of neurogenesis are characterized by highly choreographed changes in transcription factor activity. In contrast to the well-studied mechanisms of transcription factor activation during neurogenesis, much less is understood regarding how such activity is terminated. We previously showed that MTGR1, a member of the MTG family of transcriptional repressors, is strongly induced by a proneural basic helix-loop-helix transcription factor, NEUROG2 in developing nervous system. In this study, we describe a novel feedback regulation of NEUROG2 activity by MTGR1. We show that MTGR1 physically interacts with NEUROG2 and represses transcriptional activity of NEUROG2. MTGR1 also prevents DNA binding of the NEUROG2/E47 complex. In addition, we provide evidence that proper termination of NEUROG2 activity by MTGR1 is necessary for normal progression of neurogenesis in the developing spinal cord. These results highlight the importance of feedback regulation of proneural gene activity in neurodevelopment.
Bibliographical noteFunding Information:
We thank the following people for the kind gift of plasmids; Soo-Kyung Lee (Baylor College of Medicine) Sam Pfaff (Salk Institute), Masato Nakafuku (Cincinnati Children's Hospital), Atsushi Asakura (Univ. Minnesota), Klemens Meyer (Univ. Cambridge). NEUROD4 antibody is a kind gift from Thomas Jessell (Columbia Univ.) and Bennet Novitch (UCLA), anti-cNEUROG2 antibody is from David Anderson (Caltech), and anti hMTGR1 antibody is from Issay Kitabayashi (National Cancer Center Research Institute, Japan). We thank Zibing Jiang and David Hernandez for technical assistance, and Atsushi Asakura and Jonathan Slack for helpful discussions and critically reading the manuscript. DNA sequence analyses were done using resources of the Supercomputing Institute at the Univ. of Minnesota. This work was supported by Grants to NKN from Minnesota Medical Foundation, Academic Health Center, Univ. of Minnesota, Hough Parkinson's Awards, and NIH (MH078998).
- MTG/ETO proteins
- Spinal cord
- Transcriptional repressor