Feedback regulation of NEUROG2 activity by MTGR1 is required for progression of neurogenesis.
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.
Aaker
Joshua D
JD
Department of Neuroscience and Stem Cell Institute, University of Minnesota, 6-145 Jackson Hall, 321 Church St. SE, Minneapolis, MN 55455, USA.
Patineau
Andrea L
AL
Yang
Hyun-Jin
HJ
Ewart
David T
DT
Gong
Wuming
W
Li
Tongbin
T
Nakagawa
Yasushi
Y
McLoon
Steven C
SC
Koyano-Nakagawa
Naoko
N
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002642:Chick Embryo; D004247:DNA / Q000378:metabolism; D005246:Feedback; D018507:Gene Expression Regulation, Developmental; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism; D058125:Transcription Factor 7-Like 1 Protein; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; C110408:CBFA2T2 myeloid-transforming gene-related protein