- K Stefflova, D Thybert, MD Wilson, I Streeter, J Aleksic, P Karagianni, A Brazma, DJ Adams, I Talianidis, JC Marioni, P Flicek, DT Odom. Cooperativity and rapid evolution of cobound transcription factors in closely related mammals. Cell 2013;154(3):530–540. doi:10.1016/j.cell.2013.07.007
[BibTeX] [Abstract]
To mechanistically characterize the microevolutionary processes active in altering transcription factor (TF) binding among closely related mammals, we compared the genome-wide binding of three tissue-specific TFs that control liver gene expression in six rodents. Despite an overall fast turnover of TF binding locations between species, we identified thousands of TF regions of highly constrained TF binding intensity. Although individual mutations in bound sequence motifs can influence TF binding, most binding differences occur in the absence of nearby sequence variations. Instead, combinatorial binding was found to be significant for genetic and evolutionary stability; cobound TFs tend to disappear in concert and were sensitive to genetic knockout of partner TFs. The large, qualitative differences in genomic regions bound between closely related mammals, when contrasted with the smaller, quantitative TF binding differences among Drosophila species, illustrate how genome structure and population genetics together shape regulatory evolution
@Article{23911320, author = {Stefflova K and Thybert D and Wilson MD and Streeter I and Aleksic J and Karagianni P and Brazma A and Adams DJ and Talianidis I and Marioni JC and Flicek P and Odom DT}, title = {Cooperativity and rapid evolution of cobound transcription factors in closely related mammals}, journal = {Cell}, volume = {154}, number = {3}, pages = {530--540}, year = {2013}, doi = {10.1016/j.cell.2013.07.007}, abstract = {To mechanistically characterize the microevolutionary processes active in altering transcription factor (TF) binding among closely related mammals, we compared the genome-wide binding of three tissue-specific TFs that control liver gene expression in six rodents. Despite an overall fast turnover of TF binding locations between species, we identified thousands of TF regions of highly constrained TF binding intensity. Although individual mutations in bound sequence motifs can influence TF binding, most binding differences occur in the absence of nearby sequence variations. Instead, combinatorial binding was found to be significant for genetic and evolutionary stability; cobound TFs tend to disappear in concert and were sensitive to genetic knockout of partner TFs. The large, qualitative differences in genomic regions bound between closely related mammals, when contrasted with the smaller, quantitative TF binding differences among Drosophila species, illustrate how genome structure and population genetics together shape regulatory evolution},}
Description
To mechanistically characterize the microevolutionary processes active in altering transcription factor (TF) binding among closely related mammals, we compared the genome-wide binding of three tissue-specific TFs that control liver gene expression in six rodents. Despite an overall fast turnover of TF binding locations between species, we identified thousands of TF regions of highly constrained TF binding intensity. Although individual mutations in bound sequence motifs can influence TF binding, most binding differences occur in the absence of nearby sequence variations. Instead, combinatorial binding was found to be significant for genetic and evolutionary stability; cobound TFs tend to disappear in concert and were sensitive to genetic knockout of partner TFs. The large, qualitative differences in genomic regions bound between closely related mammals, when contrasted with the smaller, quantitative TF binding differences among Drosophila species, illustrate how genome structure and population genetics together shape regulatory evolution.
Raw Data
The raw chip-seq data for CEBPA, HNF4A and FOXA1 from the 5 mouse species including the CEBPA and HNF4A KO mices can be found in ArrayExpress with accession number
E-MTAB-1414.
The raw chip-seq data for CEBPA, HNF4A and FOXA1 from rat can be found in ArrayExpress with the accession number
E-MTAB-1415.
SNV data
The raw genomic data used from Keane et al (2011) used to find the SNV can be found
here
The format used for the SNV data and described below is a simplified version of pileup format:
format for a SNV: [Chromosome], [position in reference genome], [reference nt], [nt in the non reference specie]
format for an indel [Chromosome], [position in reference genome], *,[indel]
C57BL/6J vs A_J SNVs
C57BL/6J vs CAST SNVs
C57BL/6J vs SPRET SNVs
C57BL/6J vs Caroli SNVs
Fasta Files of Mouse genomes
The fasta files contain the operational genome sequences for A/J,CAST,SPRET and Caroli. The genomes were constructed for the four mouse species by interverting the single nucleotide variants (SNVs) and integrating the small indels defined above. Because of the indel insertions, the ortholog regions between the mouse reference and those genomes may not have the same coordinate. The mapping tables below allows to do the coordinate mapping.
A_J operational genome
CAST operational genome
SPRET operational genome
Caroli operational genome
Mouse strain genome alignment representation
The files below represent pairwise genome comparison defined from the SNV files described above. See the description below for the meaning of each data field:
field 1 :
chromosome
field 2 :
id (unic for 1 given chromozom)
filed 3 :
Super genome begining fragment (super genome: representation of an genome containing all insertion between two species)
field 4 :
Super genome ending fragment
field 5 :
C57BL6J start of fragment
field 6 :
C57BL6J start of insertion
field 7 :
C57BL6J ending of fragnent
field 8 :
C57BL6J ending of insertion
field 9 :
strain start of fragment
field 10 :
strain start of insertion
field 11 :
strain end of fragment
field 12 :
strain genome end of insertion
if C57BL6 or a strain has an insertion, then the start of fragment = end of fragment and the start of insertion will be 1 and the end of insertion will = to the size of insertion
C57BL/6J vs A_J mapping table
C57BL/6J vs CAST mapping table
C57BL/6J vs SPRET mapping table
C57BL/6J vs Caroli mapping table
Complete peak calls
Peaks calls made using
SWEMBL
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 wiht C57BL/6J coordinate system
intensity :
intensity in normalized read count
intensity_class :
intesnity classe
start_own :
start in specie coordinate system
end_own :
end in specie coordinate system
summit_own :
summit position in specie coordinate system
CEBPA peaks calls for 5 mouse species
HNF4A peaks calls for 5 mouse species
FOXA1 peaks calls for 5 mouse species
Peak calls with only mappable region between mouse and rat
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 wiht C57BL/6J coordinate system
start_own :
start in specie coordinate system
end_own :
end in specie coordinate system
summit_own :
summit position in specie coordinate system
CEBPA peak calls for 5 mouse species + rat
HNF4A peak calls for 5 mouse species + rat
FOXA1 peak calls for 5 mouse species + rat
Data used for motif descovery
Those fasta files contains the sequences +/-12bp around the summit of the top 2000 peaks.
CEBPA fasta file
HNF4A fasta file
FOXA1 fasta file
Motifs matrices
The position frequency matrices (PFM) used for matrix search.
Ancestral state of the union of the five mouse strains TFBRs for CEBPA, HNF4A and FOXA1
See the description below for the meaning of each data field:
field 1 :
id of the locus with format chr|start|end
field 2 :
number of most parsimonious solutions
field 3 :
intensity class in C57BL6J
field 4 :
intensity class in Anc1 , the ancestor between C57BL6 and AJ
field 5 :
intensity class in Anc2 , the ancestor between Anc1 and CAST
field 6 :
intensity class in Anc3 , the ancestor between Anc2 and SPRET
field 7 :
intensity class in Anc4 , the ancestor between Anc3 and Caroli
CEBPA ancestral state
HNF4A ancestral state
FOXA1 ancestral state