In Vivo Histone Labeling Using Ultrafast trans-Splicing Inteins

Methods Mol Biol. 2020:2133:201-219. doi: 10.1007/978-1-0716-0434-2_10.

Abstract

The development of expressed protein ligation (EPL) widened the scope of questions that could be addressed by mechanistic biochemistry. Protein trans-splicing (PTS) relies on the same basic chemical principles, but utilizes split inteins to tracelessly ligate distinct peptide or polypeptide fragments together with native peptide bonds. Here we present a method to adapt PTS methodologies for their use in live cells, in order to deliver synthetic or native histone modifications. As an example, we provide a protocol to incorporate a small molecule fluorophore into chromatinized histones. The protocol should be easily adaptable to incorporate other modifications to chromatin in vivo.

Keywords: Chromatin; In cellulo labeling; Split inteins; Synthetic biology.

Publication types

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

MeSH terms

  • Blotting, Western / methods
  • Cell Fractionation / methods
  • Cell-Penetrating Peptides / chemistry
  • Cell-Penetrating Peptides / metabolism
  • Chromatin / chemistry
  • Chromatography, High Pressure Liquid / methods
  • Chromatography, Reverse-Phase / methods
  • Disulfides / chemistry
  • Fluorescent Dyes / chemistry
  • Gene Expression
  • HEK293 Cells
  • Histones / chemistry*
  • Histones / metabolism
  • Humans
  • Inteins
  • Microscopy, Confocal
  • Nuclear Proteins / metabolism
  • Protein Splicing*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Solid-Phase Synthesis Techniques / methods*
  • Synthetic Biology / methods*
  • Transfection

Substances

  • Cell-Penetrating Peptides
  • Chromatin
  • Disulfides
  • Fluorescent Dyes
  • Histones
  • Nuclear Proteins
  • Recombinant Proteins