Transcriptional regulation of neurogenesis by the proneural factor Ascl1
Year: 2022
Type: dissertation
Abstract: This project aims to provide a better understanding of the transcriptional regulation of neurogenesis by the proneural factor Ascl1. The first genome-wide characterization of Ascl1 transcriptional program in the embryonic mouse brain was performed by ChIP-chip. However, the restriction to proximal promoter regions, excluding genes bound by Ascl1 to distal enhancers, and the need to validate the model with a more robust experimental approach, prompted the use of ChIP-seq. Genome-wide mapping of Ascl1 binding sites with higher resolution, reveals 3054 high confidence binding regions in ventral telencephalon. The chromatin states of genomic regions associated with Ascl1 recruitment were also characterised, concluding that these bear marks of distal enhancers, but also proximal promoter regions. Further integration of expression profiling data from Ascl1 LoF experiments identifies 643 target genes. Results from functional annotation of these targets corroborate previous findings, showing that Ascl1 coordinates neurogenesis by regulating a large number of target genes with a wide variety of biological functions, and associated with different stages of neurogenesis. Additional investigations should address how Ascl1 coordinates this complex transcriptional program along the neuronal lineage. This could explore a possible crosstalk with the Notch program, taking advantage of the 105 regulatory regions identified where Ascl1 is co-recruited by RBPJ, as assessed by ChIP-seq.
Author: Ribeiro, Joana Maria Martins
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W6987644894