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Waves of retrotransposon expansion remodel genome organization and CTCF binding in multiple mammalian lineages

  • [DOI] D Schmidt, PC Schwalie, MD Wilson, B Ballester, A Gonçalves, C Kutter, GD Brown, A Marshall, P Flicek, DT Odom. Waves of Retrotransposon Expansion Remodel Genome Organization and CTCF Binding in Multiple Mammalian Lineages. Cell 2012;148(1-2):335–348.
    [Bibtex]
    @Article{22244452,
    author = {Schmidt D and Schwalie PC and Wilson MD and Ballester B and Gonçalves A and Kutter C and Brown GD and Marshall A and Flicek P and Odom DT},
    title = {Waves of Retrotransposon Expansion Remodel Genome Organization and CTCF Binding in Multiple Mammalian Lineages},
    journal = {Cell},
    volume = {148},
    number = {1-2},
    pages = {335--348},
    year = {2012},
    doi = {10.1016/j.cell.2011.11.058},
    abstract = {CTCF-binding locations represent regulatory sequences that are highly constrained over the course of evolution. To gain insight into how these DNA elements are conserved and spread through the genome, we defined the full spectrum of CTCF-binding sites, including a 33/34-mer motif, and identified over five thousand highly conserved, robust, and tissue-independent CTCF-binding locations by comparing ChIP-seq data from six mammals. Our data indicate that activation of retroelements has produced species-specific expansions of CTCF binding in rodents, dogs, and opossum, which often functionally serve as chromatin and transcriptional insulators. We discovered fossilized repeat elements flanking deeply conserved CTCF-binding regions, indicating that similar retrotransposon expansions occurred hundreds of millions of years ago. Repeat-driven dispersal of CTCF binding is a fundamental, ancient, and still highly active mechanism of genome evolution in mammalian lineages. PAPERCLIP},}

As published in  Cell , a team of geneticists and computational biologists including Paul Flicek of EMBL-EBI and Duncan Odom of the WT Sanger Institute reveal how an ancient mechanism is involved in gene control and continues to drive genome evolution …  more .

Raw Data

The multi-species CTCF and SA1 ChIP-seq reads can be found in ArrayExpress with the accession number E-MTAB-437.  ChIP-seq fastq data : E-MTAB-437
The multi-species gene expression data can be found in ArrayExpress with the accession number E-MTAB-424.  RNA-seq fastq data: E-MTAB-424.

Peak calls

Peaks calls made using  SWEMBL  -R 0.005 can be found in ArrayExpress with the accession number  E-MTAB-437 , along with the raw data and are also provided below as gff files (chr, peakCaller, CTCF_species, start, end, SWEMBLScore, +, ., chr:peakSummit).

    CTCF

Peak calls for 6 species
5-way (placental) shared CTCF binding events (hg19)
Human-mouse-dog shared CTCF binding events (hg19)
5-way (placental) shared CTCF binding events (mm9)

   Cohesin (SA1)

Peak calls for opossum

Motif matrices

Below is the list of position weight matrices (PWM) for the canonical (M1) and the newly discovered (M2) CTCF motifs.
CTCF M1 and M2 PWMs
M1 PWM for each single species

    Peaks with M1 and M2 motifs

Coordinates for peaks that contain at least one M1 (NestedMica nmscan cutoff -15) and at least one M2 PWM match at a 21/22 half-site distance (included as 9 or 8 bp = distance between M1 end and M2 start).
Human peaks with both M1 and M2 PWM hits (stringent cutoff, hg19)
Human peaks with both M1 and M2 PWM hits (very lenient cutoff, hg19)
Mouse peaks with both M1 and M2 PWM hits (stringent cutoff, mm9)
Mouse peaks with both M1 and M2 PWM hits (very lenient cutoff, mm9)

The files contain coordinates of CTCF peaks and summit position, information about the M1 motif (motif column, contains chr and motif start as well as NestedMica nmscan score, with 0 the best match; if several motifs are present inside a peak they are separated by “;”) and information about M2 presence: distance from end of M1 to start of M2 (either 8 or 9), the score of M2 (0 is best match, the lower the values, the worse the match) and the strand.