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Our assays show that when SRP binding events were compared among stalled RNCs we observed an enormous range in the variance of their arrival and residence times (2.4 40.9 s and 0.4 58.7 s median arrival and residence times, respectively; Figure 1 figure supplement 3, and 'Materials and methods').
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Perinatal events were compared with neurodevelopmental outcome.
This analysis showed that on average the first SRP binding events were much delayed (∼50-fold), compared to subsequent events.
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.
Additionally, ZR75-1-specific CTCF binding events were more likely to overlap with ZR75-1-specific ER binding events (5.6%) compared to the other cell-line specific CTCF binding events (0.1% for MCF-7 specific and 0.2% for MCF10A-specific CTCF binding events).
These overlapping binding events are likely functional as they are biased towards estrogen-regulated genes, compared to regions lacking either CTCF or ER binding.
A previous study comparing CTCF binding in multiple cell types had shown that a large fraction of CTCF binding events are conserved across cell types [ 40].
Recent research showed that cooperative binding events are evolutionary much stronger conserved (Göke et al., 2011; He et al., 2011; Kazemian et al., 2013) and show a greater impact on expression compared with individual binding events (Hemberg and Kreiman, 2011).
Many protein binding events are random and inconsequential.
Proximal binding events are enriched at genes with housekeeping functions, while distal binding events interact with genes involved in dynamic biological processes including response to stimulus.
Alternatively, the two binding events are not necessarily sequential.
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