Inference of interactions between chromatin modifiers and histone modifications: from ChIP-Seq data to chromatin-signaling

Nucleic Acids Res. 2014 Dec 16;42(22):13689-95. doi: 10.1093/nar/gku1234. Epub 2014 Nov 20.

Abstract

Chromatin modifiers and histone modifications are components of a chromatin-signaling network involved in transcription and its regulation. The interactions between chromatin modifiers and histone modifications are often unknown, are based on the analysis of few genes or are studied in vitro. Here, we apply computational methods to recover interactions between chromatin modifiers and histone modifications from genome-wide ChIP-Seq data. These interactions provide a high-confidence backbone of the chromatin-signaling network. Many recovered interactions have literature support; others provide hypotheses about yet unknown interactions. We experimentally verified two of these predicted interactions, leading to a link between H4K20me1 and members of the Polycomb Repressive Complexes 1 and 2. Our results suggest that our computationally derived interactions are likely to lead to novel biological insights required to establish the connectivity of the chromatin-signaling network involved in transcription and its regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin / metabolism*
  • Chromatin Immunoprecipitation
  • Gene Expression Regulation*
  • Histones / metabolism*
  • Humans
  • K562 Cells
  • Polycomb-Group Proteins / metabolism
  • Protein Interaction Mapping / methods
  • Sequence Analysis, DNA
  • Signal Transduction

Substances

  • Chromatin
  • Histones
  • Polycomb-Group Proteins