Nucleosomes don’t have GPS, so how do they know where to go? Are they haphazardly strewn across the genome or is there some logic to it? Researchers now say they have some answers. They found that DNA sequence and DNA-binding proteins play roles in determining where nucleosomes end up, and that most nucleosomes are more consistently positioned than previously thought.
Existing data on nucleosomes are of the low-res variety, which hasn’t really helped scientists figure out where these “beads” are on the “string” of the genome. Thus, all they could say was that nucleosomes had “fuzzy,” or highly variable, positioning. Sounds like using Apple Maps in London.
This team from the U.S. and the U.K. went a major step further and created the highest-res nucleosome map ever in human cells. They used seven human lymphoblastoid cell lines, which are ideal models because the ENCODE Project has already characterized them.
The team used paired-end MNase-seq, a very precise method, to make the map, and this was the first study to do so in a human model system. Here’s what they found:
- As expected, some dinucleotides favored nucleosome formation, and nucleosomes were found in 10-bp intervals away from these dinucleotides. The data also suggested that nucleosomes were offset in some cells, but still in 10-bp intervals, preserving the rotational positioning.
- Most nucleosomes had weak positioning, but were still positioned more consistently than expected by chance. However, some (0.3%) had a very strongly consistent placement.
- Almost half of the genome had evenly spaced nucleosome arrays. Most of these regions were in heterochromatin.
- It looks like DNA-binding proteins can push nucleosomes out of the way. However, nucleosomes still end up in a periodic pattern down the strand, so DNA sequence still plays a role.
Read all the details at PLOS Genetics, November 2012.