TALE factors use two distinct functional modes to control an essential zebrafish gene expression program

Elife. 2018 Jun 18;7:e36144. doi: 10.7554/eLife.36144.

Abstract

TALE factors are broadly expressed embryonically and known to function in complexes with transcription factors (TFs) like Hox proteins at gastrula/segmentation stages, but it is unclear if such generally expressed factors act by the same mechanism throughout embryogenesis. We identify a TALE-dependent gene regulatory network (GRN) required for anterior development and detect TALE occupancy associated with this GRN throughout embryogenesis. At blastula stages, we uncover a novel functional mode for TALE factors, where they occupy genomic DECA motifs with nearby NF-Y sites. We demonstrate that TALE and NF-Y form complexes and regulate chromatin state at genes of this GRN. At segmentation stages, GRN-associated TALE occupancy expands to include HEXA motifs near PBX:HOX sites. Hence, TALE factors control a key GRN, but utilize distinct DNA motifs and protein partners at different stages - a strategy that may also explain their oncogenic potential and may be employed by other broadly expressed TFs.

Keywords: Pbx; Prep; chromatin; developmental biology; gene network; maternal regulation; pioneer factor; regenerative medicine; stem cells; zebrafish.

Publication types

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

MeSH terms

  • Animals
  • Blastula / embryology
  • Blastula / metabolism
  • CCAAT-Binding Factor / genetics
  • CCAAT-Binding Factor / metabolism
  • Gene Expression Regulation, Developmental*
  • Gene Knockdown Techniques
  • Gene Regulatory Networks
  • Genes, Essential / genetics*
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Protein Binding
  • Zebrafish / embryology
  • Zebrafish / genetics*
  • Zebrafish / metabolism
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / metabolism

Substances

  • CCAAT-Binding Factor
  • Homeodomain Proteins
  • Zebrafish Proteins