E proteins sharpen neurogenesis by modulating proneural bHLH transcription factors activity in an E-box-dependent manner
- Instituto de Biología Molecular de Barcelona, CSIC, Spain
Abstract
Class II HLH proteins heterodimerize with class I HLH/E proteins to regulate transcription. Here we show that E proteins sharpen neurogenesis by adjusting the neurogenic strength of the distinct proneural proteins. We find that inhibiting BMP signaling or its target ID2 in the chick embryo spinal cord, impairs the neuronal production from progenitors expressing ATOH1/ASCL1, but less severely that from progenitors expressing NEUROG1/2/PTF1a. We show this context-dependent response to result from the differential modulation of proneural proteins' activity by E proteins. E proteins synergize with proneural proteins when acting on CAGSTG motifs, thereby facilitating the activity of ASCL1/ATOH1 which preferentially bind to such motifs. Conversely, E proteins restrict the neurogenic strength of NEUROG1/2 by directly inhibiting their preferential binding to CADATG motifs. Since we find this mechanism to be conserved in corticogenesis, we propose this differential co-operation of E proteins with proneural proteins as a novel though general feature of their mechanism of action.
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All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
MINECO (BFU2016-81887-REDT)
- Elisa Marti
MINECO (BFU2016-77498-P)
- Elisa Marti
AECC (AIO2014)
- Gwenvael Le Dréau
CONACYT
- René Escalona
MECD (#FPU13/01384)
- Raquel Fueyo
MINECO (#FJCI-2015-26175)
- Antonio Herrera
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Le Dréau et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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E proteins sharpen neurogenesis by modulating proneural bHLH transcription factors activity in an E-box-dependent manner
eLife 7:e37267.
https://doi.org/10.7554/eLife.37267
Further reading
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