Quantitative Genetics of CTCF Binding Reveal Local Sequence Effects and Different Modes of X-Chromosome Association

Quantitative Genetics of CTCF Binding Reveal Local Sequence Effects and Different Modes of X-Chromosome Association

My first paper came out featuring work done during my PhD. The results regarding the binding of CTCF on the X chromosome is my work.

CTCF binding can be regulated by genetic variations

We have systematically measured the effect of normal genetic variation present in a human population on the binding of a specific chromatin protein (CTCF) to DNA by measuring its binding in 51 human cell lines. We observed a large number of changes in protein binding that we can confidently attribute to genetic effects. The corresponding genetic changes are often clustered around the binding motif for CTCF, but only a minority are actually within the motif.

The X chromosome and CTCF

Unexpectedly, we also find that at most binding sites on the X chromosome, CTCF binding occurs equally on both the X chromosomes in females at the same level as on the single X chromosome in males. This finding suggests that in general, CTCF binding is not subject to global dosage compensation, the process which equalizes gene expression levels from the two female X chromosomes and the single male X.

A. Plot of the metric to distinguish single-active from both active-sites, across the X chromosome for a variety of molecular assays (mRNA, ncRNA, DNase I and CTCF, coloured according to the key). B. A smooth density of the distribution of the dosage compensation fit for the 4 molecular assay types, with CTCF split into the 3 classifications (single active, both active and female specific). C. Allele-specific signal of heterozygote sites on the X chromosome from the 13 clonal female lines in the sample. The both-active sites show balanced allele-specificity, whereas the single-active sites show strong single allele CTCF binding. D. Box plot of the gender-specific behaviour of the DNase I assay at the major classes of X chromosome CTCF sites. DNase I data was collected in a different laboratory on different cell lines [17]. The both-active class shows a strong gender split, consistent with females having around double the signal, whereas the single-active sites show no gender change. doi:10.1371/journal.pgen.1004798.g005
A. Plot of the metric to distinguish single-active from both active-sites, across the X chromosome for a variety of molecular assays (mRNA, ncRNA, DNase I and CTCF, coloured according to the key). B. A smooth density of the distribution of the dosage compensation fit for the 4 molecular assay types, with CTCF split into the 3 classifications (single active, both active and female specific). C. Allele-specific signal of heterozygote sites on the X chromosome from the 13 clonal female lines in the sample. The both-active sites show balanced allele-specificity, whereas the single-active sites show strong single allele CTCF binding. D. Box plot of the gender-specific behaviour of the DNase I assay at the major classes of X chromosome CTCF sites. DNase I data was collected in a different laboratory on different cell lines [17]. The both-active class shows a strong gender split, consistent with females having around double the signal, whereas the single-active sites show no gender change.
doi:10.1371/journal.pgen.1004798.g005

Full paper

PLOS Genetics

Leave a Reply

Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.