“All men are created equal” is one of the most famous phrases in U.S. politics, but it took a while for this concept to be adopted by researchers dealing with repetitive sequences during ChIP-Seq analysis. The short length of individual deep sequencing reads creates some sequence runs that don’t map to a unique loci on a reference genome. Since repetitive sequences are often found in heterochromatic regions, this data has often been disregarded. Now, new work from a group at Cold Spring Harbor argues that this data shouldn’t be ignored in ChIP-Seq experiments.
In their study, they examined H3K9 tri-methylation with ChIP-Seq, only this time they included all repetitive sequence reads. The authors assigned the repetitive sequences to each possible alignment in the genome. Positive values were assigned to matched bases, then divided equally amongst all locations where the repetitive sequence appeared, treating each repetitive sequence as being equally responsible for the resulting sequencing read.
The results gave the team new insights into H3K9me3, suggesting that it could have a role in chromatin organization. They also learned that inclusion of this repetitive data in ChIP-Seq experiments is critical for a complete understanding of protein localization along the genome.
You can read more about this Declaration of Independence for repetitive sequences in Epigenetics, October 2009.