Clearly, the paucity of Hi C data mapping to SDs with highest se quence similarities complicates the interpretation of SD related interaction selleck compound patterns and may have compromised the precise definition of topological domains. In search of strategies which could enable us to discriminate SD Inhibitors,Modulators,Libraries associated technical artefacts from biological relevant SD insertion at domain borders, we exploited the facts that topological domains are highly conserved between mice and humans and that the syntenic region in mice lack these large SD blocks. Our cross species com parison revealed that the single copy sequences deleted in WBS indeed compose a distinct topological domain in mice, and that the large SD blocks present in humans have inserted at sites homologous to the murine domain bor ders.

This insertion of DNA sequences with different char acteristics, for example in terms of G4 motif density or preference for attachment to the nuclear membrane, could emphasise the separation of topological Inhibitors,Modulators,Libraries domains. Thus SDs may impact chromatin organisation at the level of topological domains in a way which is reminis cent of what has been proposed for pericentric SDs at the Inhibitors,Modulators,Libraries chromosomal level, namely to facilitate differential gene regulation and to protect from the regulatory influence of adjacent sequences. The reciprocal event, a dele tion of domain borders and linker region, has already been shown experimentally to provoke significant changes in the interaction pattern of two adjacent topological do mains. Further support for this assumption is pro vided by recent reports on the impact of WBS deletions on the interaction patterns of its adjacent topological domains.

Interestingly, although many SDs Inhibitors,Modulators,Libraries show accelerated rates of sequence divergence, SDs involved in the aetiology of WBS and several other genomic disorders show a con siderably high rate of gene conversion, which preserves their sequence similarity and, as a consequence, the risk of recombination events that cause the genomic disorder. On one hand, recurrent recombinations of paralogous SDs, which cause the high rate of intrachro mosomal deletions and inversions in the WBS region, supports the assumption of a high contact probability be tween these paralogous SDs within the nucleus. On the other hand, it raises the question whether sequence simi larity might serve a function that could compensate for the associated high susceptibility to structural rearrange ments mediated by SDs with high sequence similarity.

For example, SDs could influence chromatin organisation by somatic pairing as discussed above or by RNA based mechanisms. The latter option would be one explanation for the reported high transcriptional activity of pseudo genes mapping to SDs, with many of them Inhibitors,Modulators,Libraries regulated in a tissue specific figure 1 manner.