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We find a small but reproducible set of CTCF binding events that overlap with both the nuclear receptor, estrogen receptor, and the forkhead protein FOXA1.
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Events listed in the Life Events Scale included interpersonal events (such as household arguments or difficulties with partner), alongside events that overlap with PTSD items.
In the polyploid genome, we also detected 1,472 conversion events between homoeologous chromosomes, including events that overlapped 113 genes.
Additionally, to avoid confounding biased repair with initiation bias driven PRMD9 binding, we omit four events that overlap partial matches to the PRDM9 motif as described in 'Results'GC-biasedsed gene conversion').
ER/FOXA1/CTCF binding events were also significantly biased towards estrogen-regulated genes, compared to ER/FOXA1 binding events that do not have an overlapping CTCF binding event.
This overlap is higher than the number of CTCF binding events that were common to only one of the ER-positive cell lines and the ER-negative cell line (795 CTCF binding regions shared between MCF-7 and MCF10A and 1, 354 CTCF binding events shared between ZR75-1 and MCF10A), suggesting a link between CTCF and ER binding.
Additionally, in ER /AR + tumors such as the MDA-MB-453 cell line, global AR binding events largely overlap that of ER in ER + luminal A tumors [ 19].
The ATRX-binding sites that overlapped CGI promoters showed minimal overlap between the peak of ATRX binding and the CGI, indicating these overlaps may represent a distinct subclass.
Other events that partly overlapped with events 8 and 9 were found in strains E4452 and E1071 (results not shown).
As some CTCF binding events overlap with ER and FOXA1 binding events, we assessed whether the CTCF binding profile in an ER-negative cell line, lacking ER and FOXA1 expression, would differ.
Another study looking at E2F4 binding sites in seven primary mouse tissues and a mouse cell line found that between65%and85%85% of the cells' binding events overlapped [ 30], whereas a study of serum response factor (SRF) binding across three distinct human cell lines found that less than half of the observed SRF binding sites were shared across all three cell lines [ 31].
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