The Snail family transcription factor Worniu is expressed specifically in neural stem cells (NSCs), and has been previously shown to be required for larval NSC maintenance. In synthetic reporter assays the protein functions as a global repressor; however, its direct binding targets in vivo remain unknown. Here, we describe the cell-type specific genome-wide binding profiles of Worniu in third instar larval NSCs using Targeted DamID technique. We relate these binding data to larval NSC transcriptional and chromatin state data, together with previously published transcriptional profiling data for both wild-type larval NSCs, and NSCs depleted for Worniu, to identify direct transcriptional targets. We find that Worniu binds to and represses a small number of genes involved in synaptic transmission, via a novel Trithorax-repressive chromatin state. Unexpectedly, however, we show that Worniu also binds promiscuously across open chromatin within the genome, including at active promoters and enhancers, inconsistent with a role as a global repressor. Combined, we suggest a model for Worniu’s role in maintaining NSC identity within the brain.
The Snail family transcription factor Worniu is expressed specifically in neural stem cells (NSCs), and has been previously shown to be required for larval NSC maintenance. In synthetic reporter assays the protein functions as a global repressor; however, its direct binding targets in vivo remain unknown. Here, we describe the cell-type specific genome-wide binding profiles of Worniu in third instar larval NSCs using Targeted DamID technique. We relate these binding data to larval NSC transcriptional and chromatin state data, together with previously published transcriptional profiling data for both wild-type larval NSCs, and NSCs depleted for Worniu, to identify direct transcriptional targets. We find that Worniu binds to and represses a small number of genes involved in synaptic transmission, via a novel Trithorax-repressive chromatin state. Unexpectedly, however, we show that Worniu also binds promiscuously across open chromatin within the genome, including at active promoters and enhancers, inconsistent with a role as a global repressor. Combined, we suggest a model for Worniu’s role in maintaining NSC identity within the brain.
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