title: Taking into account nucleosomes for predicting gene expression.
abstract: The eukaryotic genome is organized in a chain of nucleosomes that consist of 145-147 bp of DNA wrapped around a histone octamer protein core. Binding of transcription factors (TF) to nucleosomal DNA is frequently impeded, which makes it a challenging task to calculate TF occupancy at a given regulatory genomic site for predicting gene expression. Here, we review methods to calculate TF binding to DNA in the presence of nucleosomes. The main theoretical problems are (i) the computation speed that is becoming a bottleneck when partial unwrapping of DNA from the nucleosome is considered, (ii) the perturbation of the binding equilibrium by the activity of ATP-dependent chromatin remodelers, which translocate nucleosomes along the DNA, and (iii) the model parameterization from high-throughput sequencing data and fluorescence microscopy experiments in living cells. We discuss strategies that address these issues to efficiently compute transcription factor binding in chromatin.
authors.affiliation: Research Group Genome Organization & Function, Deutsches Krebsforschungszentrum-DKFZ & BioQuant, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. V.Teif@dkfz-heidelberg.de
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Teif
authors.forename: Fabian
authors.initials: F
authors.lastname: Erdel
authors.forename: Daria A
authors.initials: DA
authors.lastname: Beshnova
authors.forename: Yevhen
authors.initials: Y
authors.lastname: Vainshtein
authors.forename: Jan-Philipp
authors.initials: JP
authors.lastname: Mallm
authors.forename: Karsten
authors.initials: K
authors.lastname: Rippe
mesh_terms: D000818:Animals; D001665:Binding Sites; D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008957:Models, Genetic; D009690:Nucleic Acid Conformation; D009707:Nucleosomes; D011485:Protein Binding; D013816:Thermodynamics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D061785:Transcription Initiation, Genetic; D015003:Yeasts / Q000235:genetics* / Q000378:metabolism
chemical_list: D009707:Nucleosomes; D014157:Transcription Factors; D004247:DNA
keywords: Chromatin; Combinatorial binding; Gene regulation function; Protein binding map; TF-nucleosome interference