title: Genome-wide in silico prediction of gene expression.
abstract: BACKGROUND
  Modelling the regulation of gene expression can provide insight into the regulatory roles of individual transcription factors (TFs) and histone modifications. Recently, Ouyang et al. in 2009 modelled gene expression levels in mouse embryonic stem (mES) cells using in vivo ChIP-seq measurements of TF binding. ChIP-seq TF binding data, however, are tissue-specific and relatively difficult to obtain. This limits the applicability of gene expression models that rely on ChIP-seq TF binding data.
  
  
  RESULTS
  In this study, we build regression-based models that relate gene expression to the binding of 12 different TFs, 7 histone modifications and chromatin accessibility (DNase I hypersensitivity) in two different tissues. We find that expression models based on computationally predicted TF binding can achieve similar accuracy to those using in vivo TF binding data and that including binding at weak sites is critical for accurate prediction of gene expression. We also find that incorporating histone modification and chromatin accessibility data results in additional accuracy. Surprisingly, we find that models that use no TF binding data at all, but only histone modification and chromatin accessibility data, can be as (or more) accurate than those based on in vivo TF binding data.
  
  
  METHODS
  All scripts, motifs and data presented in this article are available online at http://research.imb.uq.edu.au/t.bailey/supplementary_data/McLeay2011a.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Robert C
authors.initials: RC
authors.lastname: McLeay
authors.forename: Tom
authors.initials: T
authors.lastname: Lesluyes
authors.forename: Gabriel
authors.initials: G
authors.lastname: Cuellar Partida
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Bailey
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D003198:Computer Simulation; D053595:Embryonic Stem Cells / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology*; D055106:Genome-Wide Association Study / Q000379:methods*; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D016014:Linear Models; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; D014157:Transcription Factors