Feedback regulation of NEUROG2 activity by MTGR1 is required for progression of neurogenesis

Joshua D. Aaker; Andrea L. Patineau; Hyun jin Yang; David T. Ewart; Wuming Gong; Tongbin Li; Yasushi Nakagawa; Steven C. McLoon; Naoko Koyano-Nakagawa

doi:10.1016/j.mcn.2009.07.011

Feedback regulation of NEUROG2 activity by MTGR1 is required for progression of neurogenesis

Joshua D. Aaker, Andrea L. Patineau, Hyun jin Yang, David T. Ewart, Wuming Gong, Tongbin Li, Yasushi Nakagawa, Steven C. McLoon, Naoko Koyano-Nakagawa

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13 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	267-277
Number of pages	11
Journal	Molecular and Cellular Neuroscience
Volume	42
Issue number	4
DOIs	https://doi.org/10.1016/j.mcn.2009.07.011
State	Published - Nov 2009

Bibliographical note

Funding 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).

Keywords

Development
Embryo
MTG/ETO proteins
MTGR1
NEUROG2
Nervy
Neurogenesis
Spinal cord
Transcription
Transcriptional repressor
bHLH

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title = "Feedback regulation of NEUROG2 activity by MTGR1 is required for progression of neurogenesis",

abstract = "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.",

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author = "Aaker, {Joshua D.} and Patineau, {Andrea L.} and Yang, {Hyun jin} and Ewart, {David T.} and Wuming Gong and Tongbin Li and Yasushi Nakagawa and McLoon, {Steven C.} and Naoko Koyano-Nakagawa",

note = "Funding 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). ",

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AU - Li, Tongbin

AU - Nakagawa, Yasushi

AU - McLoon, Steven C.

AU - Koyano-Nakagawa, Naoko

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Feedback regulation of NEUROG2 activity by MTGR1 is required for progression of neurogenesis

Abstract

Bibliographical note

Keywords

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