RT Journal Article
SR Electronic
T1 CTCF controls imprinted gene activity at the mouse Dlk1-Dio3 and Igf2-H19 domains by modulating allele-specific sub-TAD structure
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 633065
DO 10.1101/633065
A1 David Llères
A1 Benoît Moindrot
A1 Rakesh Pathak
A1 Vincent Piras
A1 Mélody Matelot
A1 Benoît Pignard
A1 Alice Marchand
A1 Mallory Poncelet
A1 Aurélien Perrin
A1 Virgile Tellier
A1 Robert Feil
A1 Daan Noordermeer
YR 2019
UL http://biorxiv.org/content/early/2019/05/09/633065.abstract
AB Mammalian genomic imprinting is essential for development and provides a unique paradigm to explore intra-cellular differences in chromatin configuration. Here, we compared chromatin structure of the two conserved imprinted domains controlled by paternal DNA methylation imprints—the Igf2-H19 and the Dlk1-Dio3 domains—and assessed the involvement of the insulator protein CTCF. At both domains, CTCF binds the maternal allele of a differentially-methylated region (DMR), in addition to multiple instances of bi-allelic CTCF binding in their surrounding TAD (Topologically Associating Domain). On the paternal chromosome, bi-allelic CTCF binding alone is sufficient to structure a first level of sub-TAD organization. Maternal-specific CTCF binding at the DMRs adds a further layer of sub-TAD organization, which essentially hijacks the existing paternal sub-TAD organisation. Genome-editing experiments at the Dlk1-Dio3 locus confirm that the maternal sub-TADs are essential during development to maintain the imprinted Dlk1 gene in an inactive state on the maternal chromosome.