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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism*
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Cell Differentiation / physiology
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Chick Embryo
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DNA / metabolism
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Feedback*
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Gene Expression Regulation, Developmental*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Neurogenesis / physiology*
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Neurons / cytology
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Neurons / physiology
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Spinal Cord / cytology
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Spinal Cord / embryology
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Spinal Cord / metabolism
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TCF Transcription Factors / genetics
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TCF Transcription Factors / metabolism
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Transcription Factor 7-Like 1 Protein
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Transcription, Genetic
Substances
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Basic Helix-Loop-Helix Transcription Factors
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CBFA2T2 myeloid-transforming gene-related protein
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Nerve Tissue Proteins
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RNA, Small Interfering
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Repressor Proteins
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TCF Transcription Factors
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Transcription Factor 7-Like 1 Protein
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DNA