Evolution of the mammalian transcription factor binding repertoire via transposable elements

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, REL...

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Bibliographic Details
Published in:Genome Research 2008-11, Vol.18 (11), p.1752-1762
Main Authors: Bourque, Guillaume, Leong, Bernard, Vega, Vinsensius B, Chen, Xi, Lee, Yen Ling, Srinivasan, Kandhadayar G, Chew, Joon-Lin, Ruan, Yijun, Wei, Chia-Lin, Ng, Huck Hui, Liu, Edison T
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Binding Sites - genetics
Conserved Sequence
DNA - genetics
DNA - metabolism
DNA Transposable Elements - genetics
Evolution, Molecular
Humans
Letter
Mice
Repetitive Sequences, Nucleic Acid
Sequence Homology, Nucleic Acid
Transcription Factors - metabolism
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Summary: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.
ISSN:1088-9051
1549-5469
1549-5477
DOI:10.1101/gr.080663.108