GATA family members as inducers for cellular reprogramming to pluripotency

Cell Res. 2015 Feb;25(2):169-80. doi: 10.1038/cr.2015.6. Epub 2015 Jan 16.

Abstract

Members of the GATA protein family play important roles in lineage specification and transdifferentiation. Previous reports show that some members of the GATA protein family can also induce pluripotency in somatic cells by substituting for Oct4, a key pluripotency-associated factor. However, the mechanism linking lineage-specifying cues and the activation of pluripotency remains elusive. Here, we report that all GATA family members can substitute for Oct4 to induce pluripotency. We found that all members of the GATA family could inhibit the overrepresented ectodermal-lineage genes, which is consistent with previous reports indicating that a balance of different lineage-specifying forces is important for the restoration of pluripotency. A conserved zinc-finger DNA-binding domain in the C-terminus is critical for the GATA family to induce pluripotency. Using RNA-seq and ChIP-seq, we determined that the pluripotency-related gene Sall4 is a direct target of GATA family members during reprogramming and serves as a bridge linking the lineage-specifying GATA family to the pluripotency circuit. Thus, the GATA family is the first protein family of which all members can function as inducers of the reprogramming process and can substitute for Oct4. Our results suggest that the role of GATA family in reprogramming has been underestimated and that the GATA family may serve as an important mediator of cell fate conversion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Lineage
  • Cellular Reprogramming*
  • DNA / chemistry
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • GATA Transcription Factors / chemistry
  • GATA Transcription Factors / genetics
  • GATA Transcription Factors / metabolism*
  • HEK293 Cells
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism
  • LIM-Homeodomain Proteins / genetics
  • LIM-Homeodomain Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutagenesis, Site-Directed
  • Nanog Homeobox Protein
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Octamer Transcription Factor-3 / metabolism
  • Protein Binding
  • Sequence Analysis, RNA
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Zinc Fingers

Substances

  • DNA-Binding Proteins
  • Distal-less homeobox proteins
  • GATA Transcription Factors
  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Lhx5 protein, mouse
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • Nerve Tissue Proteins
  • Octamer Transcription Factor-3
  • Sall4 protein, mouse
  • Transcription Factors
  • DNA