This was consistent with the low level of pairing reported between chromosomes

To investigate this possibility, we measured the proximity of the homologous 4q and 10q Ethacridine lactate monohydrate regions. To this aim, we used the FISH technology to localize the long arms of Chlorhexidine hydrochloride chromosome 4 and 10 in interphase nuclei. Some hybridization signals were in direct contact with each other. In this case, we assumed that somatic pairing did take place. From the analysis of 200 nuclei, the level of somatic pairing ranged between 9 and 10.5% of all signals in both control and FSHD myoblasts. This was consistent with the low level of pairing reported between chromosomes 4 and 10 in a previous study. The higher pairing level observed here corresponds to the fact that, in addition to the 4q�C10q interactions, we have also revealed contacts between homologous chromosomes. From these results we can conclude that, although the existence of interactions in trans cannot be completely excluded, these do not occur in more than the 10% of the nuclei, whereas in 90% of the nuclei, the loci of interest are too far away from each other to interact. Despite many studies performed in the last twenty years, the mechanism leading to the emergence of FSHD remains poorly understood. The 3C data reported here provide the first experimental evidence that, in this genetic disease, molecular events occur that involve chromosomal segments located at a very large linear distance on the partially deleted chromosome 4q. Specifically, we have observed that in FSHD myoblasts, the subtelomeric 4qA/B marker strongly interacts with the promoter of the FRG1 gene which is located dozens of kbp proximally on the chromosome, depending on the number of remaining D4Z4 repeats. Even more strikingly, we documented a direct interaction of 4qA/B with the promoter of the ANT1 gene which lies at a linear distance greater than 5 Mbp on the centromeric side. This interaction is FSHD-specific as, in control myoblast cells, the 4qA/ B marker did not interact with the FRG1, or the ANT1 promoters. 4qA/B is a 10 kb-long polymorphic segment directly adjacent to the D4Z4 repeat array. It exists in two allelic forms, 4qA and 4qB, which are 92% identical and equally common in the general population.

Leave a Reply

Your email address will not be published.