Highly conserved sequences mediate the dynamic interplay of basic helix-loop-helix proteins regulating retinogenesis

被引:15
作者
Hernandez, Julio [1 ]
Matter-Sadzinski, Lidia [2 ]
Skowronska-Krawczyk, Dorota [2 ]
Chiodini, Florence [1 ]
Alliod, Christine [1 ]
Ballivet, Marc [1 ]
Matter, Jean-Marc [1 ,2 ]
机构
[1] Univ Geneva, Sch Med, Dept Biochem, CH-1211 Geneva, Switzerland
[2] Univ Geneva, Sch Med, Dept Ophthalmol, CH-1211 Geneva, Switzerland
关键词
D O I
10.1074/jbc.M703616200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The atonal homolog 5 (ATH5) protein is central to the transcriptional network regulating the specification of retinal ganglion cells, and its expression comes under the spatiotemporal control of several basic helix-loop-helix (bHLH) proteins in the course of retina development. Monitoring the in vivo occupancy of the ATH5 promoter by the ATH5, Ngn2, and NeuroM proteins and analyzing the DNA motifs they bind, we show that three evolutionarily conserved E-boxes are required for the bHLH proteins to control the different phases of ATH5 expression. E-box 4 mediates the activity of Ngn2, ATH5, and NeuroM along the pathway leading to the conversion of progenitors into newborn neurons. E-box 1, by mediating the antagonistic effects of Ngn2 and HES1 in proliferating progenitors, controls the expansion of the ATH5 expression domain in early retina. E-box 2 is required for the positive feedback by ATH5 that underlies the up-regulation of ATH5 expression when progenitors are going through their last cell cycle. The combinatorial nature of the regulation of the ATH5 promoter suggests that the bHLH proteins involved have no assigned E-boxes but use a common set at which they either cooperate or compete to finely tune ATH5 expression as development proceeds.
引用
收藏
页码:37894 / 37905
页数:12
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