Multi-species, multi-transcription factor binding highlights conserved control of tissue-specific biological pathways - Aix-Marseille Université Access content directly
Journal Articles eLife Year : 2014

Multi-species, multi-transcription factor binding highlights conserved control of tissue-specific biological pathways

Abstract

As exome sequencing gives way to genome sequencing, the need to interpret the function of regulatory DNA becomes increasingly important. To test whether evolutionary conservation of cis-regulatory modules (CRMs) gives insight into human gene regulation, we determined transcription factor (TF) binding locations of four liver-essential TFs in liver tissue from human, macaque, mouse, rat, and dog. Approximately, two thirds of the TF-bound regions fell into CRMs. Less than half of the human CRMs were found as a CRM in the orthologous region of a second species. Shared CRMs were associated with liver pathways and disease loci identified by genome-wide association studies. Recurrent rare human disease causing mutations at the promoters of several blood coagulation and lipid metabolism genes were also identified within CRMs shared in multiple species. This suggests that multi-species analyses of experimentally determined combinatorial TF binding will help identify genomic regions critical for tissue-specific gene control.
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Dates and versions

hal-01455448 , version 1 (03-02-2017)

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Benoit Ballester, Alejandra Medina-Rivera, Dominic Schmidt, Mar Gonzàlez-Porta, Matthew Carlucci, et al.. Multi-species, multi-transcription factor binding highlights conserved control of tissue-specific biological pathways. eLife, 2014, 462, pp.e02626. ⟨10.7554/eLife.02626.031⟩. ⟨hal-01455448⟩
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