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

Schmidt D, Schwalie PC, Wilson MD, Ballester B, Gonçalves A, Kutter C, Brown GD, Marshall A, Flicek P, Odom DT - Cell (2012)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.

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CTCF Directly Binds Specific Repeat Elements, and Mouse and Rat Share Many Bound B2 Repeat Instances, Related to Figure 4(A) Aggregate read-profiles of repeat driven CTCF-binding events in four mammals. The bars under the graphs show the density of the indicated repeats.(B) The fraction of CTCF-binding events due to B2 repeats and all other binding events in mouse (left) and rat (right) are separated into different conservation groups. A “1” indicates binding, and “0” indicates no binding in the relevant species. For example binding events that are only shared between mouse and rat are depicted as “00110” and also highlighted in red. More than half of the B2 repeats bound by CTCF in rat are also bound in mouse, indicating that the SINE transposon acquired CTCF binding in a common ancestor of rat and mouse.(C) Venn diagram showing the number of B2 repeats associated binding events in the alignable genome shared in mouse and rat.(D) Estimated ages of lineage-specific repeats that expanded CTCF binding. The white box plots are based on all instances of the indicated repeat; the red box plots are only based on repeat instances that are bound by CTCF.(E) Fraction of different CTCF-binding event categories associated with mouse (Mouse) or rodent (Rodents) specific genes.
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figs4: CTCF Directly Binds Specific Repeat Elements, and Mouse and Rat Share Many Bound B2 Repeat Instances, Related to Figure 4(A) Aggregate read-profiles of repeat driven CTCF-binding events in four mammals. The bars under the graphs show the density of the indicated repeats.(B) The fraction of CTCF-binding events due to B2 repeats and all other binding events in mouse (left) and rat (right) are separated into different conservation groups. A “1” indicates binding, and “0” indicates no binding in the relevant species. For example binding events that are only shared between mouse and rat are depicted as “00110” and also highlighted in red. More than half of the B2 repeats bound by CTCF in rat are also bound in mouse, indicating that the SINE transposon acquired CTCF binding in a common ancestor of rat and mouse.(C) Venn diagram showing the number of B2 repeats associated binding events in the alignable genome shared in mouse and rat.(D) Estimated ages of lineage-specific repeats that expanded CTCF binding. The white box plots are based on all instances of the indicated repeat; the red box plots are only based on repeat instances that are bound by CTCF.(E) Fraction of different CTCF-binding event categories associated with mouse (Mouse) or rodent (Rodents) specific genes.

Mentions: We therefore searched for an alternative mechanism for the de novo creation in a common mammalian ancestor of the thousands of CTCF-binding events now found throughout mammals. Despite the generally high conservation of CTCF motif-word usage, we noted that specific sets of motif-words were overrepresented in rodents (mouse and rat), dog, and opossum (Figure 4A). We found that the vast majority of these overrepresented motif-words are embedded within SINE transposons (Figures 4B and S4).


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

Schmidt D, Schwalie PC, Wilson MD, Ballester B, Gonçalves A, Kutter C, Brown GD, Marshall A, Flicek P, Odom DT - Cell (2012)

CTCF Directly Binds Specific Repeat Elements, and Mouse and Rat Share Many Bound B2 Repeat Instances, Related to Figure 4(A) Aggregate read-profiles of repeat driven CTCF-binding events in four mammals. The bars under the graphs show the density of the indicated repeats.(B) The fraction of CTCF-binding events due to B2 repeats and all other binding events in mouse (left) and rat (right) are separated into different conservation groups. A “1” indicates binding, and “0” indicates no binding in the relevant species. For example binding events that are only shared between mouse and rat are depicted as “00110” and also highlighted in red. More than half of the B2 repeats bound by CTCF in rat are also bound in mouse, indicating that the SINE transposon acquired CTCF binding in a common ancestor of rat and mouse.(C) Venn diagram showing the number of B2 repeats associated binding events in the alignable genome shared in mouse and rat.(D) Estimated ages of lineage-specific repeats that expanded CTCF binding. The white box plots are based on all instances of the indicated repeat; the red box plots are only based on repeat instances that are bound by CTCF.(E) Fraction of different CTCF-binding event categories associated with mouse (Mouse) or rodent (Rodents) specific genes.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3368268&req=5

figs4: CTCF Directly Binds Specific Repeat Elements, and Mouse and Rat Share Many Bound B2 Repeat Instances, Related to Figure 4(A) Aggregate read-profiles of repeat driven CTCF-binding events in four mammals. The bars under the graphs show the density of the indicated repeats.(B) The fraction of CTCF-binding events due to B2 repeats and all other binding events in mouse (left) and rat (right) are separated into different conservation groups. A “1” indicates binding, and “0” indicates no binding in the relevant species. For example binding events that are only shared between mouse and rat are depicted as “00110” and also highlighted in red. More than half of the B2 repeats bound by CTCF in rat are also bound in mouse, indicating that the SINE transposon acquired CTCF binding in a common ancestor of rat and mouse.(C) Venn diagram showing the number of B2 repeats associated binding events in the alignable genome shared in mouse and rat.(D) Estimated ages of lineage-specific repeats that expanded CTCF binding. The white box plots are based on all instances of the indicated repeat; the red box plots are only based on repeat instances that are bound by CTCF.(E) Fraction of different CTCF-binding event categories associated with mouse (Mouse) or rodent (Rodents) specific genes.
Mentions: We therefore searched for an alternative mechanism for the de novo creation in a common mammalian ancestor of the thousands of CTCF-binding events now found throughout mammals. Despite the generally high conservation of CTCF motif-word usage, we noted that specific sets of motif-words were overrepresented in rodents (mouse and rat), dog, and opossum (Figure 4A). We found that the vast majority of these overrepresented motif-words are embedded within SINE transposons (Figures 4B and S4).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.

Show MeSH