Glia-specific enhancers and chromatin structure regulate NFIA expression and glioma tumorigenesis

Stacey M. Glasgow, Jeffrey C. Carlson, Wenyi Zhu, Lesley S. Chaboub, Peng Kang, Hyun Kyoung Lee, Yoanne M. Clovis, Brittney E. Lozzi, Robert J. McEvilly, Michael G. Rosenfeld, Chad J. Creighton, Soo-Kyung Lee, Carrie A. Mohila, Benjamin Deneen

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Long-range enhancer interactions critically regulate gene expression, yet little is known about how their coordinated activities contribute to CNS development or how this may, in turn, relate to disease states. By examining the regulation of the transcription factor NFIA in the developing spinal cord, we identified long-range enhancers that recapitulate NFIA expression across glial and neuronal lineages in vivo. Complementary genetic studies found that Sox9-Brn2 and Isl1-Lhx3 regulate enhancer activity and NFIA expression in glial and neuronal populations. Chromatin conformation analysis revealed that these enhancers and transcription factors form distinct architectures within these lineages in the spinal cord. In glioma models, the glia-specific architecture is present in tumors, and these enhancers are required for NFIA expression and contribute to glioma formation. By delineating three-dimensional mechanisms of gene expression regulation, our studies identify lineage-specific chromatin architectures and associated enhancers that regulate cell fate and tumorigenesis in the CNS.

Original languageEnglish (US)
Pages (from-to)1520-1528
Number of pages9
JournalNature Neuroscience
Volume20
Issue number11
DOIs
StatePublished - 2017

ASJC Scopus subject areas

  • Neuroscience(all)

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    Glasgow, S. M., Carlson, J. C., Zhu, W., Chaboub, L. S., Kang, P., Lee, H. K., Clovis, Y. M., Lozzi, B. E., McEvilly, R. J., Rosenfeld, M. G., Creighton, C. J., Lee, S-K., Mohila, C. A., & Deneen, B. (2017). Glia-specific enhancers and chromatin structure regulate NFIA expression and glioma tumorigenesis. Nature Neuroscience, 20(11), 1520-1528. https://doi.org/10.1038/nn.4638