These studies highlighted the lack of hallmarks of CTCF-mediated domains observed in vertebrate cells. High-resolution genome-wide Hi-C maps of formaldehyde-crosslinking frequencies between pairs of DNA fragments (as a measurement of their proximity in 3D-space) were recently generated in Drosophila tissue culture cells 2, 12, 13, 14, 15. Intriguingly, although Drosophila has widespread CDs and CTCF, it is currently unclear whether CTCF-dependent domains exist in Drosophila. Overall, a large fraction of boundaries in the vertebrate genome are CTCF-dependent 9, 11. CTCF-dependent extrusion-based boundaries either reinforce or counteract compartmental domain boundaries, depending on the locus.
In vertebrates, chromosomal loops are additionally extruded on underlying compartmental domains through a process involving DNA-bound CTCF molecules which stall loop-extruding cohesin complexes at domain boundaries 1, 4, 5, 6, 7, 8, 9, 10. An evolutionarily conserved mechanism of such genome folding is thought to be compartmentalization, reflecting the segregation of chromosomal domains based on their transcriptional and epigenetic states 1, 2, 3.
Lost my ion discover dj cd series#
These results highlight a profound difference in CTCF-requirement for genome folding in flies and vertebrates, in which a large fraction of boundaries are CTCF-dependent and suggest that CTCF has played mutable roles in genome architecture and direct gene expression control during metazoan evolution.Ī wide range of animal genomes are partitioned into a series of contact domains (CDs) that exhibit increased physical proximity among loci within them. We also find that CTCF recruits the pervasive boundary-associated factor Cp190 to CTCF-occupied boundaries and co-regulates a subset of genes near boundaries together with Cp190. We find that CTCF is required to form a small fraction of all domain boundaries, while critically controlling expression patterns of certain genes and supporting nervous system function. We genetically ablate CTCF in Drosophila and examine impacts on genome folding and transcriptional regulation in the central nervous system. While Drosophila has widespread contact domains and CTCF, it is currently unclear whether CTCF-dependent domains exist in flies. Vertebrate genomes are partitioned into contact domains defined by enhanced internal contact frequency and formed by two principal mechanisms: compartmentalization of transcriptionally active and inactive domains, and stalling of chromosomal loop-extruding cohesin by CTCF bound at domain boundaries. Nature Communications volume 12, Article number: 1011 ( 2021)
CTCF loss has limited effects on global genome architecture in Drosophila despite critical regulatory functions