The GATA factor elt-1 regulates C. elegans developmental timing by promoting expression of the let-7 family microRNAs

PLoS Genet. 2015 Mar 27;11(3):e1005099. doi: 10.1371/journal.pgen.1005099. eCollection 2015 Mar.

Abstract

Postembryonic development in Caenorhabditis elegans is a powerful model for the study of the temporal regulation of development and for the roles of microRNAs in controlling gene expression. Stable switch-like changes in gene expression occur during development as stage-specific microRNAs are expressed and subsequently down-regulate other stage-specific factors, driving developmental progression. Key genes in this regulatory network are phylogenetically conserved and include the post-transcriptional microRNA repressor LIN-28; the nuclear hormone receptor DAF-12; and the microRNAs LIN-4, LET-7, and the three LET-7 family miRNAs (miR-48, miR-84, and miR-241). DAF-12 is known to regulate transcription of miR-48, miR-84 and miR-241, but its contribution is insufficient to account for all of the transcriptional regulation implied by the mutant phenotypes. In this work, the GATA-family transcription factor ELT-1 is identified from a genetic enhancer screen as a regulator of developmental timing in parallel to DAF-12, and is shown to do so by promoting the expression of the LET-7, miR-48, miR-84, and miR-241 microRNAs. The role of ELT-1 in developmental timing is shown to be separate from its role in cell-fate maintenance during post-embryonic development. In addition, analysis of Chromatin Immnoprecipitation (ChIP) data from the modENCODE project and this work suggest that the contribution of ELT-1 to the control of let-7 family microRNA expression is likely through direct transcription regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans Proteins / biosynthesis*
  • Caenorhabditis elegans Proteins / genetics
  • Cell Differentiation / genetics*
  • GATA Transcription Factors / biosynthesis*
  • GATA Transcription Factors / genetics
  • Gene Expression Regulation, Developmental
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Mutation
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Transcription, Genetic*

Substances

  • Caenorhabditis elegans Proteins
  • DAF-12 protein, C elegans
  • ELT-1 protein, C elegans
  • GATA Transcription Factors
  • MicroRNAs
  • Receptors, Cytoplasmic and Nuclear
  • let-7 microRNA, C elegans