title: Evolution of the mammalian transcription factor binding repertoire via transposable elements.
abstract: Identification of lineage-specific innovations in genomic control elements is critical for understanding transcriptional regulatory networks and phenotypic heterogeneity. We analyzed, from an evolutionary perspective, the binding regions of seven mammalian transcription factors (ESR1, TP53, MYC, RELA, POU5F1, SOX2, and CTCF) identified on a genome-wide scale by different chromatin immunoprecipitation approaches and found that only a minority of sites appear to be conserved at the sequence level. Instead, we uncovered a pervasive association with genomic repeats by showing that a large fraction of the bona fide binding sites for five of the seven transcription factors (ESR1, TP53, POU5F1, SOX2, and CTCF) are embedded in distinctive families of transposable elements. Using the age of the repeats, we established that these repeat-associated binding sites (RABS) have been associated with significant regulatory expansions throughout the mammalian phylogeny. We validated the functional significance of these RABS by showing that they are over-represented in proximity of regulated genes and that the binding motifs within these repeats have undergone evolutionary selection. Our results demonstrate that transcriptional regulatory networks are highly dynamic in eukaryotic genomes and that transposable elements play an important role in expanding the repertoire of binding sites.
authors.affiliation: Computational and Mathematical Biology, Genome Institute of Singapore, Singapore 138672, Singapore. bourque@gis.a-star.edu.sg
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bourque
authors.forename: Bernard
authors.initials: B
authors.lastname: Leong
authors.forename: Vinsensius B
authors.initials: VB
authors.lastname: Vega
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Yen Ling
authors.initials: YL
authors.lastname: Lee
authors.forename: Kandhadayar G
authors.initials: KG
authors.lastname: Srinivasan
authors.forename: Joon-Lin
authors.initials: JL
authors.lastname: Chew
authors.forename: Yijun
authors.initials: Y
authors.lastname: Ruan
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Wei
authors.forename: Huck Hui
authors.initials: HH
authors.lastname: Ng
authors.forename: Edison T
authors.initials: ET
authors.lastname: Liu
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004251:DNA Transposable Elements / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D051379:Mice; D012091:Repetitive Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004251:DNA Transposable Elements; D014157:Transcription Factors; D004247:DNA