• ES Wong, D Thybert, BM Schmitt, K Stefflova, DT Odom, P Flicek. Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals. Genome Res 2015;25(2):167–178. doi:10.1101/gr.177840.114
  [BibTeX] [Abstract]
  

  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 wildtype 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

  @Article{25394363,
  author = {Wong ES and Thybert D and Schmitt BM and Stefflova K and Odom DT and Flicek P},
  title = {Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals},
  journal = {Genome Res},
  volume = {25},
  number = {2},
  pages = {167--178},
  year = {2015},
  doi = {10.1101/gr.177840.114},
  howpublished = {Advanced online publication: 13 November 2014},
  abstract = {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 wildtype 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},}

Raw Data

The raw gene expression data for mouse species can be found in ArrayExpress  with the accesion number  E-MTAB-2483.
The raw gene expression data for HNF4A knockout can be found in ArrayExpress with the accession number  E-MTAB-2484.

Processed data

Processed gene expression data and list of target genes can be found  here .

R code

Snippets of R code for analyses detailed in the manuscript can be found  here .

Complete peak calls

Datasets are from  “Cooperativity and rapid evolution of cobound transcription factors in closely related mammals” , Stefflova and Thybert et al. Cell 2013, and processed as described in their manuscript.
See the description below for the meaning of each data field:

chr:  chromosome
start_bl6 :  start of binding region wiht C57BL/6J coordinate system
end_bl6 :  start of binding region wiht C57BL/6J coordinate system
summit_bl6 :  summit of binding region with C57BL/6J coordinate system
intensity :  intensity in normalized read count
intensity_class :  intensity class
start_own :  start in species coordinate system
end_own :  end in species coordinate system
summit_own :  summit position in specie coordinate system

CEBPA peak calls for 5 mouse species
HNF4A peak calls for 5 mouse species
FOXA1 peak calls for 5 mouse species

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