RESUMEN
The generation of neurons from neural stem cells requires large-scale changes in gene expression that are controlled to a large extent by proneural transcription factors, such as Ascl1. While recent studies have characterized the differentiation genes activated by proneural factors, less is known on the mechanisms that suppress progenitor cell identity. Here, we show that Ascl1 induces the transcription factor MyT1 while promoting neuronal differentiation. We combined functional studies of MyT1 during neurogenesis with the characterization of its transcriptional program. MyT1 binding is associated with repression of gene transcription in neural progenitor cells. It promotes neuronal differentiation by counteracting the inhibitory activity of Notch signaling at multiple levels, targeting the Notch1 receptor and many of its downstream targets. These include regulators of the neural progenitor program, such as Hes1, Sox2, Id3, and Olig1. Thus, Ascl1 suppresses Notch signaling cell-autonomously via MyT1, coupling neuronal differentiation with repression of the progenitor fate.
Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Diferenciación Celular/genética , Proteínas de Unión al ADN/genética , Neurogénesis/genética , Receptor Notch1/genética , Factores de Transcripción/genética , Animales , Regulación del Desarrollo de la Expresión Génica , Proteínas Inhibidoras de la Diferenciación/genética , Ratones , Células-Madre Neurales/citología , Células-Madre Neurales/metabolismo , Neuronas/metabolismo , Factores de Transcripción SOXB1/genética , Células Madre/citología , Células Madre/metabolismo , Factor de Transcripción HES-1/genética , Vertebrados/genética , Vertebrados/crecimiento & desarrolloRESUMEN
The cytochrome PccH from Geobacter sulfurreducens (Gs) plays a crucial role in current-consuming fumarate-reducing biofilms. Deletion of pccH gene inhibited completely electron transfer from electrodes toward Gs cells. The pccH gene was cloned and the protein heterologously expressed in Escherichia coli. Complementary biophysical techniques including CD, UV-visible and NMR spectroscopy were used to characterize PccH. This cytochrome contains one low-spin c-type heme with His-Met axial coordination and unusual low-reduction potential. This reduction potential is pH-dependent, within the Gs physiological pH range, and is discussed within the context of the electron transfer mechanisms from electrodes to Gs cells.