author_facet Wong, Emily S.
Thybert, David
Schmitt, Bianca M.
Stefflova, Klara
Odom, Duncan T.
Flicek, Paul
Wong, Emily S.
Thybert, David
Schmitt, Bianca M.
Stefflova, Klara
Odom, Duncan T.
Flicek, Paul
author Wong, Emily S.
Thybert, David
Schmitt, Bianca M.
Stefflova, Klara
Odom, Duncan T.
Flicek, Paul
spellingShingle Wong, Emily S.
Thybert, David
Schmitt, Bianca M.
Stefflova, Klara
Odom, Duncan T.
Flicek, Paul
Genome Research
Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals
Genetics (clinical)
Genetics
author_sort wong, emily s.
spelling Wong, Emily S. Thybert, David Schmitt, Bianca M. Stefflova, Klara Odom, Duncan T. Flicek, Paul 1088-9051 1549-5469 Cold Spring Harbor Laboratory Genetics (clinical) Genetics http://dx.doi.org/10.1101/gr.177840.114 <jats:p>To understand the evolutionary dynamics between transcription factor (TF) binding and gene expression in mammals, we compared transcriptional output and the binding intensities for three tissue-specific TFs in livers from four closely related mouse species. For each transcription factor, TF-dependent genes and the TF binding sites most likely to influence mRNA expression were identified by comparing mRNA expression levels between wild-type and TF knockout mice. Independent evolution was observed genome-wide between the rate of change in TF binding and the rate of change in mRNA expression across taxa, with the exception of a small number of TF-dependent genes. We also found that binding intensities are preferentially conserved near genes whose expression is dependent on the TF, and the conservation is shared among binding peaks in close proximity to each other near the TSS. Expression of TF-dependent genes typically showed an increased sensitivity to changes in binding levels as measured by mRNA abundance. Taken together, these results highlight a significant tolerance to evolutionary changes in TF binding intensity in mammalian transcriptional networks and suggest that some TF-dependent genes may be largely regulated by a single TF across evolution.</jats:p> Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals Genome Research
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title Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals
title_unstemmed Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals
title_full Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals
title_fullStr Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals
title_full_unstemmed Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals
title_short Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals
title_sort decoupling of evolutionary changes in transcription factor binding and gene expression in mammals
topic Genetics (clinical)
Genetics
url http://dx.doi.org/10.1101/gr.177840.114
publishDate 2015
physical 167-178
description <jats:p>To understand the evolutionary dynamics between transcription factor (TF) binding and gene expression in mammals, we compared transcriptional output and the binding intensities for three tissue-specific TFs in livers from four closely related mouse species. For each transcription factor, TF-dependent genes and the TF binding sites most likely to influence mRNA expression were identified by comparing mRNA expression levels between wild-type and TF knockout mice. Independent evolution was observed genome-wide between the rate of change in TF binding and the rate of change in mRNA expression across taxa, with the exception of a small number of TF-dependent genes. We also found that binding intensities are preferentially conserved near genes whose expression is dependent on the TF, and the conservation is shared among binding peaks in close proximity to each other near the TSS. Expression of TF-dependent genes typically showed an increased sensitivity to changes in binding levels as measured by mRNA abundance. Taken together, these results highlight a significant tolerance to evolutionary changes in TF binding intensity in mammalian transcriptional networks and suggest that some TF-dependent genes may be largely regulated by a single TF across evolution.</jats:p>
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author Wong, Emily S., Thybert, David, Schmitt, Bianca M., Stefflova, Klara, Odom, Duncan T., Flicek, Paul
author_facet Wong, Emily S., Thybert, David, Schmitt, Bianca M., Stefflova, Klara, Odom, Duncan T., Flicek, Paul, Wong, Emily S., Thybert, David, Schmitt, Bianca M., Stefflova, Klara, Odom, Duncan T., Flicek, Paul
author_sort wong, emily s.
container_issue 2
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container_title Genome Research
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description <jats:p>To understand the evolutionary dynamics between transcription factor (TF) binding and gene expression in mammals, we compared transcriptional output and the binding intensities for three tissue-specific TFs in livers from four closely related mouse species. For each transcription factor, TF-dependent genes and the TF binding sites most likely to influence mRNA expression were identified by comparing mRNA expression levels between wild-type and TF knockout mice. Independent evolution was observed genome-wide between the rate of change in TF binding and the rate of change in mRNA expression across taxa, with the exception of a small number of TF-dependent genes. We also found that binding intensities are preferentially conserved near genes whose expression is dependent on the TF, and the conservation is shared among binding peaks in close proximity to each other near the TSS. Expression of TF-dependent genes typically showed an increased sensitivity to changes in binding levels as measured by mRNA abundance. Taken together, these results highlight a significant tolerance to evolutionary changes in TF binding intensity in mammalian transcriptional networks and suggest that some TF-dependent genes may be largely regulated by a single TF across evolution.</jats:p>
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spelling Wong, Emily S. Thybert, David Schmitt, Bianca M. Stefflova, Klara Odom, Duncan T. Flicek, Paul 1088-9051 1549-5469 Cold Spring Harbor Laboratory Genetics (clinical) Genetics http://dx.doi.org/10.1101/gr.177840.114 <jats:p>To understand the evolutionary dynamics between transcription factor (TF) binding and gene expression in mammals, we compared transcriptional output and the binding intensities for three tissue-specific TFs in livers from four closely related mouse species. For each transcription factor, TF-dependent genes and the TF binding sites most likely to influence mRNA expression were identified by comparing mRNA expression levels between wild-type and TF knockout mice. Independent evolution was observed genome-wide between the rate of change in TF binding and the rate of change in mRNA expression across taxa, with the exception of a small number of TF-dependent genes. We also found that binding intensities are preferentially conserved near genes whose expression is dependent on the TF, and the conservation is shared among binding peaks in close proximity to each other near the TSS. Expression of TF-dependent genes typically showed an increased sensitivity to changes in binding levels as measured by mRNA abundance. Taken together, these results highlight a significant tolerance to evolutionary changes in TF binding intensity in mammalian transcriptional networks and suggest that some TF-dependent genes may be largely regulated by a single TF across evolution.</jats:p> Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals Genome Research
spellingShingle Wong, Emily S., Thybert, David, Schmitt, Bianca M., Stefflova, Klara, Odom, Duncan T., Flicek, Paul, Genome Research, Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals, Genetics (clinical), Genetics
title Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals
title_full Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals
title_fullStr Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals
title_full_unstemmed Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals
title_short Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals
title_sort decoupling of evolutionary changes in transcription factor binding and gene expression in mammals
title_unstemmed Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals
topic Genetics (clinical), Genetics
url http://dx.doi.org/10.1101/gr.177840.114