Autor: |
Fraser J; The School of Biomedical Sciences, The University of Queensland, Brisbane, 4072, Australia., Essebier A; The School of Chemistry and Molecular Bioscience, The University of Queensland, Brisbane, 4072, Australia., Brown AS; Department of Developmental Biology, School of Medicine, Stanford University, Stanford, CA, USA., Davila RA; The School of Biomedical Sciences, The University of Queensland, Brisbane, 4072, Australia., Harkins D; The School of Biomedical Sciences, The University of Queensland, Brisbane, 4072, Australia., Zalucki O; The School of Biomedical Sciences, The University of Queensland, Brisbane, 4072, Australia., Shapiro LP; Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Penzes P; Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Wainwright BJ; Institute for Molecular Bioscience, The University of Queensland, Brisbane, 4072, Australia., Scott MP; Department of Developmental Biology, School of Medicine, Stanford University, Stanford, CA, USA., Gronostajski RM; Department of Biochemistry, Program in Genetics, Genomics and Bioinformatics, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, NY, USA., Bodén M; The School of Chemistry and Molecular Bioscience, The University of Queensland, Brisbane, 4072, Australia., Piper M; The School of Biomedical Sciences, The University of Queensland, Brisbane, 4072, Australia. m.piper@uq.edu.au.; Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Australia. m.piper@uq.edu.au., Harvey TJ; The School of Biomedical Sciences, The University of Queensland, Brisbane, 4072, Australia. t.harvey1@uq.edu.au. |
Abstrakt: |
Transcriptional regulation plays a central role in controlling neural stem and progenitor cell proliferation and differentiation during neurogenesis. For instance, transcription factors from the nuclear factor I (NFI) family have been shown to co-ordinate neural stem and progenitor cell differentiation within multiple regions of the embryonic nervous system, including the neocortex, hippocampus, spinal cord and cerebellum. Knockout of individual Nfi genes culminates in similar phenotypes, suggestive of common target genes for these transcription factors. However, whether or not the NFI family regulates common suites of genes remains poorly defined. Here, we use granule neuron precursors (GNPs) of the postnatal murine cerebellum as a model system to analyse regulatory targets of three members of the NFI family: NFIA, NFIB and NFIX. By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development. |