A concentration of 0.1 mg per milliliter initiates co-localization during X-chromosome inactivation, according to PLoS paper.

A research group has discovered that a thermodynamic switch pulls together X chromosomes in female cells at a crucial stage of embryo development. They report that only once the level of a protein called CTCF reaches 0.1 mg per milliliter can X chromosomes pair up during X-chromosome inactivation, a process of that ensures that the levels of X-derived products are equalized in XX females and XY males.

The scientists decided to look at a particular DNA-specific binding molecule, a protein known as CTCF, that seemed to play a role in pairing off of X chromosomes. Previously, in the presence of mutated CTCF or deleted sections of DNA to which CTCF binds, pairing, or co-localization of the X chromosomes, was disrupted.

To study how exactly CTCF had this effect, the investigators created a model of the interaction between X chromosomes and CTCF proteins using polymer physics. They looked at models of chains of polymer beads that had almost the same number of chemical binding sites on their beads as the number of known CTCF binding sites in the key part of X chromosomes.

They found that a key tipping point was reached if the amount of CTCF present in the system reached a critical threshold: a concentration of around 0.1 mg per milliliter. Below that point very little happened. Random bindings did occur but not often enough or quickly enough to build the sort of momentum necessary to produce the total and suddenness of X-chromosomes co-localization required for successful X inactivation.

Once the threshold concentration was reached, however, a thermodynamic switch was triggered. That particular concentration of CTCF was suddenly enough to ensure that the CTCF proteins could encounter and bind in quick succession to two X chromosomes forming a chemical bridge between them and almost instantly bringing about co-localization of the X chromosomes and making embryo development successful.

The researchers believe that this newly discovered thermodynamic switch could also apply to a range of other cell processes that involve the recognition and pairing of DNA sequences, including other homologous chromosomes.

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