title: CORECLUST: identification of the conserved CRM grammar together with prediction of gene regulation.
abstract: Identification of transcriptional regulatory regions and tracing their internal organization are important for understanding the eukaryotic cell machinery. Cis-regulatory modules (CRMs) of higher eukaryotes are believed to possess a regulatory 'grammar', or preferred arrangement of binding sites, that is crucial for proper regulation and thus tends to be evolutionarily conserved. Here, we present a method CORECLUST (COnservative REgulatory CLUster STructure) that predicts CRMs based on a set of positional weight matrices. Given regulatory regions of orthologous and/or co-regulated genes, CORECLUST constructs a CRM model by revealing the conserved rules that describe the relative location of binding sites. The constructed model may be consequently used for the genome-wide prediction of similar CRMs, and thus detection of co-regulated genes, and for the investigation of the regulatory grammar of the system. Compared with related methods, CORECLUST shows better performance at identification of CRMs conferring muscle-specific gene expression in vertebrates and early-developmental CRMs in Drosophila.
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 1-73 Leninskie Gory, Moscow 119991, Russia. nikanka@bioinf.fbb.msu.ru
authors.forename: Anna A
authors.initials: AA
authors.lastname: Nikulova
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Favorov
authors.forename: Roman A
authors.initials: RA
authors.lastname: Sutormin
authors.forename: Vsevolod J
authors.initials: VJ
authors.lastname: Makeev
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Mironov
mesh_terms: D000465:Algorithms; D000818:Animals; D019521:Body Patterning / Q000235:genetics; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D009132:Muscles / Q000378:metabolism; D056510:Position-Specific Scoring Matrices; D050436:Regulatory Elements, Transcriptional; D017422:Sequence Analysis, DNA; D012984:Software