Rbpj direct regulation of Atoh7 transcription in the embryonic mouse retina

• Published in: Scientific reports Vol. 8; no. 1; pp. 10195 - 13
• Main Authors: Miesfeld, Joel B., Moon, Myung-soon, Riesenberg, Amy N., Contreras, Ashley N., Kovall, Rhett A., Brown, Nadean L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.07.2018; Nature Publishing Group
• Subjects: 38; 38/1; 631/136/368/2430; 631/45/612/822; 64/60; 82/51; 96/106; Binding sites; Calorimetry; Chromatin; Embryos; Gene regulation; Humanities and Social Sciences; Immunoprecipitation; multidisciplinary; Neural stem cells; Notch1 protein; Progenitor cells; Retina; Retinal ganglion cells; Science; Science (multidisciplinary); Signal transduction; Stem cells; Transcription
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-28420-y

In vertebrate retinal progenitor cells, the proneural factor Atoh7 exhibits a dynamic tissue and cellular expression pattern. Although the resulting Atoh7 retinal lineage contains all seven major cell types, only retinal ganglion cells require Atoh7 for proper differentiation. Such specificity necessitates complex regulation of Atoh7 transcription during retina development. The Notch signaling pathway is an evolutionarily conserved suppressor of proneural bHLH factor expression. Previous in vivo mouse genetic studies established the cell autonomous suppression of Atoh7 transcription by Notch1 , Rbpj and Hes1 . Here we identify four CSL binding sites within the Atoh7 proximal regulatory region and demonstrate Rbpj protein interaction at these sequences by in vitro electromobility shift, calorimetry and luciferase assays and, in vivo via colocalization and chromatin immunoprecipitation. We found that Rbpj simultaneously represses Atoh7 t ranscription using both Notch-dependent and –independent pathways.