Poly(ADP-ribosyl)ation associated changes in CTCF-chromatin binding and gene expression in breast cells

Ioanna Pavlaki, France Docquier, Igor Chernukhin, Georgia Kita, Svetlana Gretton, Christopher T. Clarkson, Vladimir B. Teif, Elena Klenova

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

CTCF is an evolutionarily conserved and ubiquitously expressed architectural protein regulating a plethora of cellular functions via different molecular mechanisms. CTCF can undergo a number of post-translational modifications which change its properties and functions. One such modifications linked to cancer is poly(ADP-ribosyl)ation (PARylation). The highly PARylated CTCF form has an apparent molecular mass of 180 kDa (referred to as CTCF180), which can be distinguished from hypo- and non-PARylated CTCF with the apparent molecular mass of 130 kDa (referred to as CTCF130). The existing data accumulated so far have been mainly related to CTCF130. However, the properties of CTCF180 are not well understood despite its abundance in a number of primary tissues. In this study we performed ChIP-seq and RNA-seq analyses in human breast cells 226LDM, which display predominantly CTCF130 when proliferating, but CTCF180 upon cell cycle arrest. We observed that in the arrested cells the majority of sites lost CTCF, whereas fewer sites gained CTCF or remain bound (i.e. common sites). The classical CTCF binding motif was found in the lost and common, but not in the gained sites. The changes in CTCF occupancies in the lost and common sites were associated with increased chromatin densities and altered expression from the neighboring genes. Based on these results we propose a model integrating the CTCF130/180 transition with CTCF-DNA binding and gene expression changes. This study also issues an important cautionary note concerning the design and interpretation of any experiments using cells and tissues where CTCF180 may be present.

Original languageEnglish
Pages (from-to)718-730
Number of pages13
JournalBBA - Gene Regulatory Mechanisms
Volume1861
Issue number8
Early online date25 Jul 2018
DOIs
Publication statusPublished - 1 Aug 2018

Keywords

  • Breast/drug effects
  • CCCTC-Binding Factor/metabolism
  • Cell Line
  • Chromatin/metabolism
  • DNA/chemistry
  • Female
  • Gene Expression
  • Humans
  • Hydroxyurea/pharmacology
  • Nocodazole/pharmacology
  • Nucleosomes/metabolism
  • Nucleotide Motifs
  • Poly ADP Ribosylation

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biophysics
  • Structural Biology
  • Biochemistry

Cite this

Pavlaki, I., Docquier, F., Chernukhin, I., Kita, G., Gretton, S., Clarkson, C. T., Teif, V. B., & Klenova, E. (2018). Poly(ADP-ribosyl)ation associated changes in CTCF-chromatin binding and gene expression in breast cells. BBA - Gene Regulatory Mechanisms, 1861(8), 718-730. https://doi.org/10.1016/j.bbagrm.2018.06.010