Functions of FACT in Breaking the Nucleosome and Maintaining Its Integrity at the Single-Nucleosome Level

Mol Cell. 2018 Jul 19;71(2):284-293.e4. doi: 10.1016/j.molcel.2018.06.020.


The human FACT (facilitates chromatin transcription) complex, composed of two subunits SPT16 (Suppressor of Ty 16) and SSRP1 (Structure-specific recognition protein-1), plays essential roles in nucleosome remodeling. However, the molecular mechanism of FACT reorganizing the nucleosome still remains elusive. In this study, we demonstrate that FACT displays dual functions in destabilizing the nucleosome and maintaining the original histones and nucleosome integrity at the single-nucleosome level. We found that the subunit SSRP1 is responsible for maintenance of nucleosome integrity by holding the H3/H4 tetramer on DNA and promoting the deposition of the H2A/H2B dimer onto the nucleosome. In contrast, the large subunit SPT16 destabilizes the nucleosome structure by displacing the H2A/H2B dimers. Our findings provide mechanistic insights by which the two subunits of FACT coordinate with each other to fulfill its functions and suggest that FACT may play essential roles in preserving the original histones with epigenetic identity during transcription or DNA replication.

Keywords: FACT complex; SPT16; SSRP1; magnetic tweezers; nucleosome integrity; nucleosome stability; original histone; single nucleosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Chromatin / metabolism
  • DNA / metabolism
  • DNA Replication
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism*
  • Histones / metabolism
  • Humans
  • Models, Molecular
  • Nucleosomes / genetics
  • Nucleosomes / metabolism*
  • Protein Binding
  • Protein Multimerization
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sf9 Cells
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Elongation Factors / genetics
  • Transcriptional Elongation Factors / metabolism*


  • Cell Cycle Proteins
  • Chromatin
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Histones
  • Nucleosomes
  • SPT16 protein, S cerevisiae
  • SSRP1 protein, human
  • SUPT16H protein, human
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Transcriptional Elongation Factors
  • DNA