Identification of highly conserved putative developmental enhancers bound by SOX3 in neural progenitors using ChIP-Seq

Abstract

The transcription factor SOX3 is expressed within most neural progenitor (NP) cells of the vertebrate central nervous system (CNS) and is essential for normal brain development in mice and humans. However, despite the widespread expression of Sox3, CNS defects in null mice are relatively mild due to functional redundancy with the other SOXB1 sub-group members Sox1 and Sox2. To further understand the molecular function of SOX3, we investigated the genome-wide binding profile of endogenous SOX3 in NP cells using ChIP-seq. SOX3 binding was identified at over 8,000 sites, most of which were intronic or intergeneic and were significantly associated with neurodevelopmental genes. The majority of binding sites were moderately or highly conserved (phastCons scores .0.1 and 0.5, respectively) and included the previously characterised, SOXB1-binding Nestin NP cell enhancer. Comparison of SOX3 and published ChIP-Seq data for the co-activator P300 in embryonic brain identified hundreds of highly conserved putative enhancer elements. In addition, we identified a subset of highly conserved putative enhancers for CNS development genes common to SOXB1 members in NP cells, all of which contained the SOX consensus motif (ACAAWR). Together these data implicate SOX3 in the direct regulation of hundreds of NP genes and provide molecular insight into the overlapping roles of SOXB1 proteins in CNS development.