Reciprocal autoregulation by NFI occupancy and ETV1 promotes the developmental expression of dendrite-synapse genes in cerebellar granule neurons Academic Article uri icon

Overview

MeSH Major

  • DNA-Binding Proteins
  • NFI Transcription Factors
  • Transcription Factors

abstract

  • Nuclear Factor One (NFI) transcription factors regulate temporal gene expression required for dendritogenesis and synaptogenesis via delayed occupancy of target promoters in developing cerebellar granule neurons (CGNs). Mechanisms that promote NFI temporal occupancy have not been previously defined. We show here that the transcription factor ETV1 directly binds to and is required for expression and NFI occupancy of a cohort of NFI-dependent genes in CGNs maturing in vivo. Expression of ETV1 is low in early postnatal cerebellum and increases with maturation, mirroring NFI temporal occupancy of coregulated target genes. Precocious expression of ETV1 in mouse CGNs accelerated onset of expression and NFI temporal occupancy of late target genes and enhanced Map2(+) neurite outgrowth. ETV1 also activated expression and NFI occupancy of the Etv1 gene itself, and this autoregulatory loop preceded ETV1 binding and activation of other coregulated target genes in vivo. These findings suggest a potential model in which ETV1 activates NFI temporal binding to a subset of late-expressed genes in a stepwise manner by initial positive feedback regulation of the Etv1 gene itself followed by activation of downstream coregulated targets as ETV1 expression increases. Sequential transcription factor autoregulation and subsequent binding to downstream promoters may provide an intrinsic developmental timer for dendrite/synapse gene expression.

publication date

  • May 2016

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4850036

Digital Object Identifier (DOI)

  • 10.1091/mbc.E15-07-0476

PubMed ID

  • 26941328

Additional Document Info

start page

  • 1488

end page

  • 99

volume

  • 27

number

  • 9