Repression by PRDM13 is critical for generating precise neuronal identity (RNA-Seq)

The mechanisms that activate some genes while silencing others are critical to ensure precision in lineage specification as multipotent progenitors become restricted in cell fate. During neurodevelopment, these mechanisms are required to generate the wide variety of neuronal subtypes found in the nervous system. Here we report interactions between basic helix-loop-helix (bHLH) transcriptional activators and the transcriptional repressor PRDM13 that are critical for these processes during specification of dorsal spinal cord neurons. PRDM13 inhibits gene expression programs for the excitatory neuronal lineages in the dorsal neural tube while also suppressing a battery of genes that determine ventral neural tube fates including Olig1, Olig2 and Prdm12. PRDM13 does this via recruitment to chromatin by multiple neural bHLH factors to restrict gene expression in specific neuronal lineages. Together these findings highlight the function of PRDM13 in repressing bHLH transcriptional activators that together are required to achieve precise neuronal specification during development. Overall design: RNA-seq analysis performed on GFP+ cells sorted by FACS from Prdm13GFP/+ or Prdm13GFP/GFP mouse E11.5 neural tubes to identify gene expression in the presence and absence of PRDM13.

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Mona B, Uruena A, Kollipara RK, Ma Z, Borromeo MD, Chang JC, Johnson JE