Binding profiles of chromatin-modifying proteins are predictive for transcriptional activity and promoter-proximal pausing

J Comput Biol. 2012 Feb;19(2):126-38. doi: 10.1089/cmb.2011.0258.

Abstract

The establishment and maintenance of proper gene expression patterns is essential for stable cell differentiation. Using unsupervised learning techniques, chromatin states have been linked to discrete gene expression states, but these models cannot predict continuous gene expression levels, nor do they reveal detailed insight into the chromatin-based control of gene expression. Here, we employ regularized regression techniques to link, in a quantitative manner, binding profiles of chromatin proteins to gene expression levels and promoter-proximal pausing of RNA polymerase II in Drosophila melanogaster on a genome-wide scale. We apply stability selection to reliably detect interactions of chromatin features and predict several known, suggested, and novel proteins and protein pairs as transcriptional activators or repressors. Our integrative analysis reveals new insights into the complex interplay of transcriptional regulators in the context of gene expression. Supplementary Material is available at www.libertonline.com/cmb.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Computer Simulation*
  • Data Interpretation, Statistical
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Gene Expression Regulation*
  • Linear Models
  • Models, Genetic*
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism
  • Regression Analysis
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transcriptional Activation

Substances

  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Drosophila Proteins
  • Transcription Factors
  • RNA Polymerase II