3D genomic architecture and transcriptional regulation

Nano-HiC: HiC coupled with nanopore to capture single-cell gene conformations.

Dosage Compensation (DC) in Caenorhabditis elegans is achieved by half-repression of X-linked genes on both X chromosomes in the hermaphrodites (XX) as compared to the males (X). This reduction of gene expression is associated with the formation of enhanced Topologically Associated Domains (eTADs). TADs are defined as highly self-contacting portions of the genome, delimited by boundaries enriched with structural maintenance complexes (SMC).

TADs show variability in internal contact frequency; some TADs display high contact frequencies while in others these contacts are sparse. The level of TAD internal contacts can be used as a measure of chromatin compaction, which in turn can be correlated with changes in gene transcription.

eTADs in C. elegans result from the combined action of the Dosage Compensation Complex (DCC), an SMC complex, and highly oriented sequence motifs called rex sites. However, the question remains on how loading of the DCC induces changes of the chromosome structure and the correlation with gene expression regulation. Therefore, the formation of the eTAD exclusively on the X chromosome in the hermaphrodites and its dependence on DC provides the perfect system to decipher if and how these domains regulate transcription.

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