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

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) bindin...

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Autores principales: Ballester, Benoit, Medina-Rivera, Alejandra, Schmidt, Dominic, Gonzàlez-Porta, Mar, Carlucci, Matthew, Chen, Xiaoting, Chessman, Kyle, Faure, Andre J, Funnell, Alister PW, Goncalves, Angela, Kutter, Claudia, Lukk, Margus, Menon, Suraj, McLaren, William M, Stefflova, Klara, Watt, Stephen, Weirauch, Matthew T, Crossley, Merlin, Marioni, John C, Odom, Duncan T, Flicek, Paul, Wilson, Michael D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359374/
https://www.ncbi.nlm.nih.gov/pubmed/25279814
http://dx.doi.org/10.7554/eLife.02626
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author Ballester, Benoit
Medina-Rivera, Alejandra
Schmidt, Dominic
Gonzàlez-Porta, Mar
Carlucci, Matthew
Chen, Xiaoting
Chessman, Kyle
Faure, Andre J
Funnell, Alister PW
Goncalves, Angela
Kutter, Claudia
Lukk, Margus
Menon, Suraj
McLaren, William M
Stefflova, Klara
Watt, Stephen
Weirauch, Matthew T
Crossley, Merlin
Marioni, John C
Odom, Duncan T
Flicek, Paul
Wilson, Michael D
author_facet Ballester, Benoit
Medina-Rivera, Alejandra
Schmidt, Dominic
Gonzàlez-Porta, Mar
Carlucci, Matthew
Chen, Xiaoting
Chessman, Kyle
Faure, Andre J
Funnell, Alister PW
Goncalves, Angela
Kutter, Claudia
Lukk, Margus
Menon, Suraj
McLaren, William M
Stefflova, Klara
Watt, Stephen
Weirauch, Matthew T
Crossley, Merlin
Marioni, John C
Odom, Duncan T
Flicek, Paul
Wilson, Michael D
author_sort Ballester, Benoit
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.02626.001
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spelling pubmed-43593742015-03-16 Multi-species, multi-transcription factor binding highlights conserved control of tissue-specific biological pathways Ballester, Benoit Medina-Rivera, Alejandra Schmidt, Dominic Gonzàlez-Porta, Mar Carlucci, Matthew Chen, Xiaoting Chessman, Kyle Faure, Andre J Funnell, Alister PW Goncalves, Angela Kutter, Claudia Lukk, Margus Menon, Suraj McLaren, William M Stefflova, Klara Watt, Stephen Weirauch, Matthew T Crossley, Merlin Marioni, John C Odom, Duncan T Flicek, Paul Wilson, Michael D eLife Genomics and Evolutionary Biology 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. DOI: http://dx.doi.org/10.7554/eLife.02626.001 eLife Sciences Publications, Ltd 2014-10-03 /pmc/articles/PMC4359374/ /pubmed/25279814 http://dx.doi.org/10.7554/eLife.02626 Text en © 2014, Ballester et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Genomics and Evolutionary Biology
Ballester, Benoit
Medina-Rivera, Alejandra
Schmidt, Dominic
Gonzàlez-Porta, Mar
Carlucci, Matthew
Chen, Xiaoting
Chessman, Kyle
Faure, Andre J
Funnell, Alister PW
Goncalves, Angela
Kutter, Claudia
Lukk, Margus
Menon, Suraj
McLaren, William M
Stefflova, Klara
Watt, Stephen
Weirauch, Matthew T
Crossley, Merlin
Marioni, John C
Odom, Duncan T
Flicek, Paul
Wilson, Michael D
Multi-species, multi-transcription factor binding highlights conserved control of tissue-specific biological pathways
title Multi-species, multi-transcription factor binding highlights conserved control of tissue-specific biological pathways
title_full Multi-species, multi-transcription factor binding highlights conserved control of tissue-specific biological pathways
title_fullStr Multi-species, multi-transcription factor binding highlights conserved control of tissue-specific biological pathways
title_full_unstemmed Multi-species, multi-transcription factor binding highlights conserved control of tissue-specific biological pathways
title_short Multi-species, multi-transcription factor binding highlights conserved control of tissue-specific biological pathways
title_sort multi-species, multi-transcription factor binding highlights conserved control of tissue-specific biological pathways
topic Genomics and Evolutionary Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359374/
https://www.ncbi.nlm.nih.gov/pubmed/25279814
http://dx.doi.org/10.7554/eLife.02626
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