Combining Cell Fate Reprogramming and Protein Engineering to Study Transcription Factor Functions

Methods Mol Biol. 2021:2352:227-236. doi: 10.1007/978-1-0716-1601-7_15.

Abstract

Gene expression regulation by transcription factors plays a central role in determining and maintaining cell fate during normal development as well as induced cell fate reprogramming. Induction of cell identity-determining gene regulatory networks by reprogramming factors that act as transcriptional activators is key to induce desired cell fates. Conversely, repression of unwanted genetic programs by transcriptional repressors is equally important to ensure cell fate fidelity. Here we describe engineering techniques to create fusion proteins that allow exploration of the major transcriptional contribution (activation or repression) of specific neuronal reprogramming factors during direct cell fate conversion. This method can be extended to every reprogramming regime to enable the functional categorization of any transcription factor.

Keywords: Cell fate conversion; Chimeric protein; Fusion protein; Neuronal reprogramming; Protein engineering; Structure function; Transcription factor; Transcriptional activator; Transcriptional repressor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation* / genetics
  • Cellular Reprogramming Techniques*
  • Cellular Reprogramming*
  • Cloning, Molecular
  • Gene Expression
  • Gene Expression Regulation, Developmental
  • Humans
  • Protein Engineering* / methods
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Analysis, DNA
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Recombinant Fusion Proteins
  • Transcription Factors