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KLF6 and STAT3 co-occupy regulatory DNA and functionally synergize to promote axon growth in CNS neurons.

Scientific reports | 2018

The failure of axon regeneration in the CNS limits recovery from damage and disease. Members of the KLF family of transcription factors can exert both positive and negative effects on axon regeneration, but the underlying mechanisms are unclear. Here we show that forced expression of KLF6 promotes axon regeneration by corticospinal tract neurons in the injured spinal cord. RNA sequencing identified 454 genes whose expression changed upon forced KLF6 expression in vitro, including sub-networks that were highly enriched for functions relevant to axon extension including cytoskeleton remodeling, lipid synthesis, and bioenergetics. In addition, promoter analysis predicted a functional interaction between KLF6 and a second transcription factor, STAT3, and genome-wide footprinting using ATAC-Seq data confirmed frequent co-occupancy. Co-expression of the two factors yielded a synergistic elevation of neurite growth in vitro. These data clarify the transcriptional control of axon growth and point the way toward novel interventions to promote CNS regeneration.

Pubmed ID: 30135567 RIS Download

Associated grants

  • Agency: U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS), International
    Id: NS093278
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS083983
  • Agency: U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS), International
    Id: NS083983
  • Agency: NINDS NIH HHS, United States
    Id: R21 NS093278
  • Agency: Craig H. Neilsen Foundation, International
    Id: Project Number 385379

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This is a list of tools and resources that we have found mentioned in this publication.


GraphPad Prism (tool)

RRID:SCR_002798

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RRID:SCR_005736

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RRID:SCR_001575

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RRID:SCR_005748

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RRID:SCR_014583

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