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Publication : Isl1 and Pou4f2 form a complex to regulate target genes in developing retinal ganglion cells.

First Author  Li R Year  2014
Journal  PLoS One Volume  9
Issue  3 Pages  e92105
PubMed ID  24643061 Mgi Jnum  J:239195
Mgi Id  MGI:5825419 Doi  10.1371/journal.pone.0092105
Citation  Li R, et al. (2014) Isl1 and Pou4f2 form a complex to regulate target genes in developing retinal ganglion cells. PLoS One 9(3):e92105
abstractText  Precise regulation of gene expression during biological processes, including development, is often achieved by combinatorial action of multiple transcription factors. The mechanisms by which these factors collaborate are largely not known. We have shown previously that Isl1, a Lim-Homeodomain transcription factor, and Pou4f2, a class IV POU domain transcription factor, co-regulate a set of genes required for retinal ganglion cell (RGC) differentiation. Here we further explore how these two factors interact to precisely regulate gene expression during RGC development. By GST pulldown assays, co-immunoprecipitation, and electrophoretic mobility shift assays, we show that Isl1 and Pou4f2 form a complex in vitro and in vivo, and identify the domains within these two proteins that are responsible for this interaction. By luciferase assay, in situ hybridization, and RNA-seq, we further demonstrate that the two factors contribute quantitatively to gene expression in the developing RGCs. Although each factor alone can activate gene expression, both factors are required to achieve optimal expression levels. Finally, we discover that Isl1 and Pou4f2 can interact with other POU and Lim-Homeodomain factors respectively, indicating the interactions between these two classes of transcription factors are prevalent in development and other biological processes.
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