Abstract

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Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery, thereby controlling gene expression. BRG1/BRM associated factor (BAF) chromatin remodeling complexes are polymorphic assemblies of up to 15 subunits encoded by several genes. We have identified that ‚Äãone BAF complex protein, Dpf2, is expressed as a different isoform in neurons that can potentially target the BAF complex to new loci as a part of the neuronal program of gene expression. This new isoform (Dpf2-L) is a longer splice variant generated by alternative splicing (AS), a mechanism that allows multiple transcripts to be produced from a single gene. The Dpf2-L isoform differs from the canonical Dpf2-S isoform in the inclusion of exon 7, which incorporates 14 additional amino acids into the C2H2-type zinc finger domain of the Dpf2 protein. RT-PCR of RNAs from mouse cortex over the course of development from E15 to P60, showed a shift in splicing from the canonical Dpf2-S to the Dpf2-L isoform during brain development. We observed a similar splicing shift towards the Dpf2-L isoform in cultured cortical neurons at different time points. We also observed a decrease in overall Dpf2 protein expression as cultured cortical neurons mature. Although the canonical short isoform (Dpf2-S) has already been demonstrated in maintaining embryonic stem cell pluripotency, the functional differences between the two isoforms are still largely unknown. The switch in expression suggests that Dpf2-L may play a pivotal role in epigenetic regulation during neuronal development.