Charakterisierung des regulatorischen Netzwerkes von ST18 in der Neurogenese
Entwicklungsbiologie
Zusammenfassung der Projektergebnisse
Specification of neuronal fate during development relies on a precisely controlled gene expression program. Despite progress, the repertoire of transcription factors involved in transcriptional reprogramming underlying neurogenesis remains largely unexplored. We applied a comprehensive bioinformatics approach to reveal potential novel transcription factors regulating neuronal development. For one such factor, St18, we revealed neuronal lineage specific expression pattern accompanied with transient induction during neurogenesis. Such expression pattern suggested a pivotal role during a defined time window during neuronal differentiation and further analysis suggested that St18 seems to be specifically induced by the neuronal transcription factor NeuroD1. Depletion of St18 compromises neurogenesis and causes deregulation of genes essential for acquisition of post-mitotic neuronal fate and we provide evidence that St18 regulates genes involved in cell cycle regulation. Mechanistically St18 interacts with members of chromatin repressive machinery such as Lsd1, HDACs and RBPs. For a subset of genes that are upregulated upon St18 depletion in vivo we show that St18 is required for proper recruitment of Lsd1 during neuronal differentiation to their promoters in order to cause chromatin compaction and transcriptional repression. Our findings so far establish St18 as a novel potential transcriptional repressor that functions during onset of neurogenesis to ensure repression of target genes through recruitment of chromatin repressive machinery in order to establish timely acquisition of post-mitotic and early neuronal fate.
