Expression of FACT in mammalian tissues suggests its role in maintaining of undifferentiated state of cells

Oncotarget. 2011 Oct;2(10):783-96. doi: 10.18632/oncotarget.340.

Abstract

The Facilitates Chromatin Transcription (FACT) chromatin remodeling complex, comprised of two subunits, SSRP1 and SPT16, is involved in transcription, replication and DNA repair. We recently showed that curaxins, small molecules with anti-cancer activity, target FACT and kill tumor cells in a FACT-dependent manner. We also found that FACT is overexpressed in human and mouse tumors and that tumor cells are sensitive to FACT downregulation. To clarify the clinical potential of FACT inhibition, we were interested in physiological role(s) of FACT in multicellular organisms. We analyzed SSRP1 and SPT16 expression in different cells, tissues and conditions using Immunohistochemical (IHC) staining of mouse and human tissues and analysis of publically available high-content gene expression datasets. Both approaches demonstrated coordinated expression of the two FACT subunits, which was primarily associated with the stage of cellular differentiation. Most cells of adult tissues do not have detectable protein level of FACT. High FACT expression was associated with stem or less-differentiated cells, while low FACT levels were seen in more differentiated cells. Experimental manipulation of cell differentiation and proliferation in vitro, as well as tissue staining for the Ki67 proliferation marker, showed that FACT expression is related more to differentiation than to proliferation. Thus, FACT may be part of a stem cell-like gene expression signature and play a role in maintaining cells in an undifferentiated state, which is consistent with its potential role as an anti-cancer target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation*
  • Cell Proliferation*
  • Cells, Cultured
  • Chromatin / physiology*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Female
  • Fibrosarcoma / genetics*
  • Fibrosarcoma / metabolism
  • Fibrosarcoma / pathology
  • High Mobility Group Proteins / genetics*
  • High Mobility Group Proteins / metabolism
  • Humans
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Male
  • Mice
  • Myoblasts / cytology
  • Myoblasts / metabolism*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transcriptional Elongation Factors / genetics*
  • Transcriptional Elongation Factors / metabolism

Substances

  • Cell Cycle Proteins
  • Chromatin
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Ki-67 Antigen
  • SSRP1 protein, human
  • SUPT16H protein, human
  • Supt16 protein, mouse
  • Transcription Factors
  • Transcriptional Elongation Factors