"G4 binding activities in genomic regulators of nucleosome remodeling, paraspeckle assembly, RNA splicing, and three-dimensional genome organization. Among the prominent hits, we identify the genomic architectural protein, CCCTC-binding factor (CTCF), as one of the strongest G4 binders.
The latter function is crucial, as it reflects the ability of G4 structures to regulate large-scale chromosomal structures:
G-quadruplexes interact with several nuclear protein complexes involved in crucial genomic processes. We found that the genomic architectural protein, CCCTC-binding factor (CTCF), directly binds to G4s and this interaction is important for regulation of genome topology and gene expression. Our work uncovers the architectural roles of G4 structures in the genome and contributes important insights into G4 biology and 3D genome organization.
At the scale of tens to hundreds of kilobases, the genome is further assembled into self-interacting regions known as topologically associating domains (TADs), with higher propensity of genomic interactions observed within, rather than between TADs.
TADs mediate enhancer–promoter interactions and are important for cell-type specific gene expression programs. Interestingly, G4s are shown to be enriched at TAD boundaries and implicated in regulating insulation strength of TADs.
The paper proposes a model that involves CTCF–G4 interaction in mediating long-range chromatin looping to define stable chromatin loops or boundaries of topologically associating domains (TADs).he point being: repetitive DNA helps form non-B DNA shapes like G4s, and these G4s are crucial for defining TADs which help define the 3D structure of the genome, regulating gene expression and even defining cell types. Far from being junk, this repetitive DNA is crucial for formatting the genome."
CaseyLuskin
The paper proposes a model that involves CTCF–G4 interaction in mediating long-range chromatin looping to define stable chromatin loops or boundaries of topologically associating domains (TADs).he point being: repetitive DNA helps form non-B DNA shapes like G4s, and these G4s are crucial for defining TADs which help define the 3D structure of the genome, regulating gene expression and even defining cell types. Far from being junk, this repetitive DNA is crucial for formatting the genome."
CaseyLuskin
