TY - JOUR TI - E proteins sharpen neurogenesis by modulating proneural bHLH transcription factors’ activity in an E-box-dependent manner AU - Le Dréau, Gwenvael AU - Escalona, René AU - Fueyo, Raquel AU - Herrera, Antonio AU - Martínez, Juan D AU - Usieto, Susana AU - Menendez, Anghara AU - Pons, Sebastian AU - Martinez-Balbas, Marian A AU - Marti, Elisa A2 - Nathans, Jeremy A2 - Bronner, Marianne E VL - 7 PY - 2018 DA - 2018/08/10 SP - e37267 C1 - eLife 2018;7:e37267 DO - 10.7554/eLife.37267 UR - https://doi.org/10.7554/eLife.37267 AB - 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. KW - E proteins KW - proneural proteins KW - neurogenesis KW - neuronal differentiation KW - ID proteins KW - bone morphogenetic proteins JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -