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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 Occupancy in Five Placental Mammalian Genomes Reveals a Large Core Set of Conserved Binding(A) The total numbers of CTCF-binding events found in orthologous locations between each pair of placental species are shown as row-column intersections. The right-most numbers for each species represent all alignable CTCF-binding peaks (total peaks are in parentheses). Percentages are percentage-averages between pairwise species (Experimental Procedures).(B) Five-way comparison of CTCF binding in five placental mammals identified a shared set of 5,178 CTCF-binding events.(C) The upper track shows CTCF binding after CTCF knockdown (CTCF) in human MCF-7 cells (Figure S1F). The track immediately below shows CTCF binding with control RNAi (mock). The bottom five tracks show CTCF-binding data in liver of five mammalian species in syntenic regions, demonstrating that highly conserved CTCF-binding events are less sensitive to perturbation by RNAi knockdown.(D) The fraction of binding events found only in human (human only) or shared among all placental (five-way) were characterized by their sensitivity to RNAi knockdown of CTCF protein. Very few deeply shared CTCF-binding events were affected by CTCF knockdown.(E) Relation between motif information content and motif sequence conservation for nine TFs in human. (F) Relation between motif length and motif sequence conservation for the same TFs as in (E).See also Figure S1 and Table S2.
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fig1: CTCF Occupancy in Five Placental Mammalian Genomes Reveals a Large Core Set of Conserved Binding(A) The total numbers of CTCF-binding events found in orthologous locations between each pair of placental species are shown as row-column intersections. The right-most numbers for each species represent all alignable CTCF-binding peaks (total peaks are in parentheses). Percentages are percentage-averages between pairwise species (Experimental Procedures).(B) Five-way comparison of CTCF binding in five placental mammals identified a shared set of 5,178 CTCF-binding events.(C) The upper track shows CTCF binding after CTCF knockdown (CTCF) in human MCF-7 cells (Figure S1F). The track immediately below shows CTCF binding with control RNAi (mock). The bottom five tracks show CTCF-binding data in liver of five mammalian species in syntenic regions, demonstrating that highly conserved CTCF-binding events are less sensitive to perturbation by RNAi knockdown.(D) The fraction of binding events found only in human (human only) or shared among all placental (five-way) were characterized by their sensitivity to RNAi knockdown of CTCF protein. Very few deeply shared CTCF-binding events were affected by CTCF knockdown.(E) Relation between motif information content and motif sequence conservation for nine TFs in human. (F) Relation between motif length and motif sequence conservation for the same TFs as in (E).See also Figure S1 and Table S2.

Mentions: The inclusion of rat and macaque allowed us to compare closely related species, which overlapped by up to 60% in shared CTCF binding. In fact, as might be expected, CTCF-binding divergence generally corresponded with evolutionary distance (Figure 1A).


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 Occupancy in Five Placental Mammalian Genomes Reveals a Large Core Set of Conserved Binding(A) The total numbers of CTCF-binding events found in orthologous locations between each pair of placental species are shown as row-column intersections. The right-most numbers for each species represent all alignable CTCF-binding peaks (total peaks are in parentheses). Percentages are percentage-averages between pairwise species (Experimental Procedures).(B) Five-way comparison of CTCF binding in five placental mammals identified a shared set of 5,178 CTCF-binding events.(C) The upper track shows CTCF binding after CTCF knockdown (CTCF) in human MCF-7 cells (Figure S1F). The track immediately below shows CTCF binding with control RNAi (mock). The bottom five tracks show CTCF-binding data in liver of five mammalian species in syntenic regions, demonstrating that highly conserved CTCF-binding events are less sensitive to perturbation by RNAi knockdown.(D) The fraction of binding events found only in human (human only) or shared among all placental (five-way) were characterized by their sensitivity to RNAi knockdown of CTCF protein. Very few deeply shared CTCF-binding events were affected by CTCF knockdown.(E) Relation between motif information content and motif sequence conservation for nine TFs in human. (F) Relation between motif length and motif sequence conservation for the same TFs as in (E).See also Figure S1 and Table S2.
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Related In: Results  -  Collection

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fig1: CTCF Occupancy in Five Placental Mammalian Genomes Reveals a Large Core Set of Conserved Binding(A) The total numbers of CTCF-binding events found in orthologous locations between each pair of placental species are shown as row-column intersections. The right-most numbers for each species represent all alignable CTCF-binding peaks (total peaks are in parentheses). Percentages are percentage-averages between pairwise species (Experimental Procedures).(B) Five-way comparison of CTCF binding in five placental mammals identified a shared set of 5,178 CTCF-binding events.(C) The upper track shows CTCF binding after CTCF knockdown (CTCF) in human MCF-7 cells (Figure S1F). The track immediately below shows CTCF binding with control RNAi (mock). The bottom five tracks show CTCF-binding data in liver of five mammalian species in syntenic regions, demonstrating that highly conserved CTCF-binding events are less sensitive to perturbation by RNAi knockdown.(D) The fraction of binding events found only in human (human only) or shared among all placental (five-way) were characterized by their sensitivity to RNAi knockdown of CTCF protein. Very few deeply shared CTCF-binding events were affected by CTCF knockdown.(E) Relation between motif information content and motif sequence conservation for nine TFs in human. (F) Relation between motif length and motif sequence conservation for the same TFs as in (E).See also Figure S1 and Table S2.
Mentions: The inclusion of rat and macaque allowed us to compare closely related species, which overlapped by up to 60% in shared CTCF binding. In fact, as might be expected, CTCF-binding divergence generally corresponded with evolutionary distance (Figure 1A).

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