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.
- Elisa Marti
- Elisa Marti
- Gwenvael Le Dréau
- René Escalona
- Raquel Fueyo
- Antonio Herrera
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Jeremy Nathans, Reviewing Editor, Johns Hopkins University School of Medicine, United States
- Received: April 5, 2018
- Accepted: August 9, 2018
- Accepted Manuscript published: August 10, 2018 (version 1)
© 2018, Le Dréau et al.
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