Common Regulatory Targets of NFIA, NFIX and NFIB during Postnatal Cerebellar Development.

Cerebellum (London, England) 2020 Feb

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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.

Citation

James Fraser, Alexandra Essebier, Alexander S Brown, Raul Ayala Davila, Danyon Harkins, Oressia Zalucki, Lauren P Shapiro, Peter Penzes, Brandon J Wainwright, Matthew P Scott, Richard M Gronostajski, Mikael Bodén, Michael Piper, Tracey J Harvey. Common Regulatory Targets of NFIA, NFIX and NFIB during Postnatal Cerebellar Development. Cerebellum (London, England). 2020 Feb;19(1):89-101