Multi-omics dissection of 3D chromosome structure perturbations in patient-derived cells: lessons from imprinting disorders DAAN NOORDERMEER, Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell, France
Donderdag 22 oktober, 11u00
The ~ 100 imprinted genes in mammalian genomes are mono-allelically expressed based on their parental origin (i.e. they are only active on the chromosome inherited from the mother or father). Many of these genes cluster together in 20 imprinted domains where dedicated regulatory elements, the so-called “Imprinting Control Regions” (ICRs), dictate allele-specific transcriptional activity throughout the domain. The ICRs at all domains are distinguished by allele-specific DNA methylation, but how they transmit their regulatory instructions over distance differs from one domain to the other. At a subset of imprinted domains, this regulation involves DNA methylation-dependent binding of the CTCF insulator protein to the ICR. We previously showed in mouse cells that CTCF binding at ICRs creates differential 3D chromatin structure, whereby the formation of allele-specific TADs (Topologically Associating Domains) permit rewiring of enhancer-promoter contacts.
