The basic body plan and major physiological axes have been highly conserved during mammalian evolution, yet only a small fraction of the human genome sequence appears to be subject to evolutionary constraint. To quantify cis- versus trans-acting contributions to mammalian regulatory evolution, we performed genomic DNase I footprinting of the mouse genome across 25 cell and tissue types, collectively defining sim8.6 million transcription factor (TF) occupancy sites at nucleotide resolution. Here we show that mouse TF footprints conjointly encode a regulatory lexicon that is sim95% similar with that derived from human TF footprints. However, only sim20% of mouse TF footprints have human orthologues. Despite substantial turnover of the cis-regulatory landscape, nearly half of all pairwise regulatory interactions connecting mouse TF genes have been maintained in orthologous human cell types through evolutionary innovation of TF recognition sequences. Furthermore, the higher-level organization of mouse TF-to-TF connections into cellular network architectures is nearly identical with human. Our results indicate that evolutionary selection on mammalian gene regulation is targeted chiefly at the level of trans-regulatory circuitry, enabling and potentiating cis-regulatory plasticity.
%0 Journal Article
%1 stergachis2014conservation
%A Stergachis, Andrew B.
%A Neph, Shane
%A Sandstrom, Richard
%A Haugen, Eric
%A Reynolds, Alex P.
%A Zhang, Miaohua
%A Byron, Rachel
%A Canfield, Theresa
%A Stelhing-Sun, Sandra
%A Lee, Kristen
%A Thurman, Robert E.
%A Vong, Shinny
%A Bates, Daniel
%A Neri, Fidencio
%A Diegel, Morgan
%A Giste, Erika
%A Dunn, Douglas
%A Vierstra, Jeff
%A Hansen, R. Scott
%A Johnson, Audra K.
%A Sabo, Peter J.
%A Wilken, Matthew S.
%A Reh, Thomas A.
%A Treuting, Piper M.
%A Kaul, Rajinder
%A Groudine, Mark
%A Bender, M. A.
%A Borenstein, Elhanan
%A Stamatoyannopoulos, John A.
%D 2014
%I Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
%J Nature
%K regulatory_evolution regulatory_networks regulatory_sequence_turnover
%N 7527
%P 365--370
%T Conservation of trans-acting circuitry during mammalian regulatory evolution
%U http://dx.doi.org/10.1038/nature13972
%V 515
%X The basic body plan and major physiological axes have been highly conserved during mammalian evolution, yet only a small fraction of the human genome sequence appears to be subject to evolutionary constraint. To quantify cis- versus trans-acting contributions to mammalian regulatory evolution, we performed genomic DNase I footprinting of the mouse genome across 25 cell and tissue types, collectively defining sim8.6 million transcription factor (TF) occupancy sites at nucleotide resolution. Here we show that mouse TF footprints conjointly encode a regulatory lexicon that is sim95% similar with that derived from human TF footprints. However, only sim20% of mouse TF footprints have human orthologues. Despite substantial turnover of the cis-regulatory landscape, nearly half of all pairwise regulatory interactions connecting mouse TF genes have been maintained in orthologous human cell types through evolutionary innovation of TF recognition sequences. Furthermore, the higher-level organization of mouse TF-to-TF connections into cellular network architectures is nearly identical with human. Our results indicate that evolutionary selection on mammalian gene regulation is targeted chiefly at the level of trans-regulatory circuitry, enabling and potentiating cis-regulatory plasticity.
@article{stergachis2014conservation,
abstract = {The basic body plan and major physiological axes have been highly conserved during mammalian evolution, yet only a small fraction of the human genome sequence appears to be subject to evolutionary constraint. To quantify cis- versus trans-acting contributions to mammalian regulatory evolution, we performed genomic DNase I footprinting of the mouse genome across 25 cell and tissue types, collectively defining [sim]8.6 million transcription factor (TF) occupancy sites at nucleotide resolution. Here we show that mouse TF footprints conjointly encode a regulatory lexicon that is [sim]95% similar with that derived from human TF footprints. However, only [sim]20% of mouse TF footprints have human orthologues. Despite substantial turnover of the cis-regulatory landscape, nearly half of all pairwise regulatory interactions connecting mouse TF genes have been maintained in orthologous human cell types through evolutionary innovation of TF recognition sequences. Furthermore, the higher-level organization of mouse TF-to-TF connections into cellular network architectures is nearly identical with human. Our results indicate that evolutionary selection on mammalian gene regulation is targeted chiefly at the level of trans-regulatory circuitry, enabling and potentiating cis-regulatory plasticity.},
added-at = {2017-06-15T18:27:10.000+0200},
author = {Stergachis, Andrew B. and Neph, Shane and Sandstrom, Richard and Haugen, Eric and Reynolds, Alex P. and Zhang, Miaohua and Byron, Rachel and Canfield, Theresa and Stelhing-Sun, Sandra and Lee, Kristen and Thurman, Robert E. and Vong, Shinny and Bates, Daniel and Neri, Fidencio and Diegel, Morgan and Giste, Erika and Dunn, Douglas and Vierstra, Jeff and Hansen, R. Scott and Johnson, Audra K. and Sabo, Peter J. and Wilken, Matthew S. and Reh, Thomas A. and Treuting, Piper M. and Kaul, Rajinder and Groudine, Mark and Bender, M. A. and Borenstein, Elhanan and Stamatoyannopoulos, John A.},
biburl = {https://www.bibsonomy.org/bibtex/288d5a74208771af81a40cb2f67b17d93/peter.ralph},
interhash = {d35fe86d2e92152e8079026530114a1c},
intrahash = {88d5a74208771af81a40cb2f67b17d93},
issn = {00280836},
journal = {Nature},
keywords = {regulatory_evolution regulatory_networks regulatory_sequence_turnover},
month = nov,
number = 7527,
pages = {365--370},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
timestamp = {2017-06-15T18:27:10.000+0200},
title = {Conservation of trans-acting circuitry during mammalian regulatory evolution},
url = {http://dx.doi.org/10.1038/nature13972},
volume = 515,
year = 2014
}