However, the effects of PTMs on the genome-wide binding of CTCF and the organization of three-dimensional (3D) chromatin structure have not been fully understood.
a, Schematic structure of the CTCF ZFs.DNA binding is recognized by ZF3–ZF7. Black circles mark dinucleotides that might contain a CpG and thus have the potential to carry 5meC, which can ...
Using an integrated 3D NucleOme Modeling Engine (3D-NOME) that builds a hierarchical tree structure to represent the 3D genome with increasing resolution ... we simulated the 3D genome models from the combined CTCF and RNAPII ChIA-PET data derived from GM12878. In these models, several known chromosomal features were captured, e.g., ...
These observations solidify what now appears to be one of the underlying principles by which the orientation of the DNA sequence in CTCF binding sites shapes 3D genome organization. However, this new finding raises a series of questions as to the mechanisms underlying the specificity of interactions between CTCF sites in the genome ...
CTCF and cohesin organize the 3D eukaryotic genome. Zhang et al. report direct single-molecule and structure evidence that CTCF is a polar cohesin barrier. R-loops are also cohesin barriers and likely play a role in organizing the 3D genome.
Furthermore, we show that haplotype variants and allelic interactions have differential effects on chromosome configuration, influencing gene expression, and may provide mechanistic insights into functions associated with disease susceptibility. 3D genome simulation suggests a model of chromatin folding around chromosomal axes, where CTCF is ...
The 3D genome organization and its dynamic modulate genome function, playing a pivotal role in cell differentiation and development. CTCF and cohesin, acting as the core architectural components involved in chromatin looping and genome folding, can also recruit other protein or RNA partners to fine-tune genome structure during development.
Graph representation of 3D-genome based on CTCF-segments. We segmented the chromatin based on CTCF-binding peaks. Each fragment corresponds to a vertex, ... TADs are known as the elementary 3D structure of chromatin with a crucial role in transcriptional regulation . TADs are isolated from each other at the boundary ends.
The molecular mechanism of how cohesin and CTCF structure the 3D genome has remained unclear. Here we show that a segment within the CTCF N terminus interacts with the SA2–SCC1 subunits of human ...
The architectural protein CTCF plays a complex role in decoding the functional output of the genome. Guo et al. now show that the orientation of a CTCF site restricts its choice of interacting partner, thus creating a code that predicts the three-dimensional organization of the genome. We propose a DNA extrusion model to account for orientation-specific loop formation.
VI. 3D genome models elucidate the human genome structure and function. Using an integrated 3D NucleOme Modeling Engine (3D-NOME) that builds a hierarchical tree structure to represent the 3D genome with increasing resolution (Figure S7A-C) (Szalaj et al., In preparation), we simulated the 3D genome models from the combined CTCF and RNAPII ChIA ...
GAM is a ligation-free technology which captures long-range chromatin interactions spanning whole chromosomes and has revealed extensive specificity in the 3D chromatin structure of specific cell types (Beagrie et al, 2017; Beagrie et al, 2023; Winick-Ng et al, 2021; Fiorillo et al, 2021).GAM measures 3D genome topology by sequencing the DNA content from a collection of thin (~200 nm) nuclear ...
Abstract. The 3D genome organization and its dynamic modulate genome function, playing a pivotal role in cell differentiation and development. CTCF and cohesin, acting as the core architectural components involved in chromatin looping and genome folding, can also recruit other protein or RNA partners to fine-tune genome structure during development.
MIT Associate Professor Bin Zhang takes a computational approach to studying the 3D structure of the genome: He uses computer simulations and generative AI to understand how a 2-meter-long string of DNA manages to fit inside a cell’s nucleus.
CCCTC-binding factor (CTCF) is a critical regulator of chromatin architecture, which underlies its functions that include gene expression and three-dimensional (3D) genome construction and regulation [19–22]. In mammals, CTCF recognizes chromatin insulators to segment chromatin into several TADs.
The three-dimensional configuration of the genome ensures cell type-specific gene expression profiles by placing genes and regulatory elements in close spatial proximity. ... (in situ Hi-C), RNA sequencing (RNA-seq) and chromatin immunoprecip … Integrative analysis of the 3D genome structure reveals that CTCF maintains the properties of mouse ...
Cohesin and CTCF emerge as building blocks of 3D genome structure. ... Cohesin and CTCF emerge as building blocks of 3D genome structure Nat Rev Genet. 2025 Feb;26(2):80. doi: 10.1038/s41576-024-00795-x. Author Julia Horsfield 1 Affiliation 1 Department of Pathology, Dunedin ...
If DNA-bound CTCF is able to diffuse unrestrictedly in the 3D space to encounter the second loop anchor at tens or hundreds of kilobases away, the orientation of the CTCF-bound motif should be ...
The field has taken a great leap forward with the advent of molecular methods designed to ‘capture’ contacts between DNA fragments in their native 3D state, effectively describing the conformation of chromosomes .The extensive coverage and high-resolution nature of subsequent genomic methods such as Hi-C and 4C-seq are refining our understanding of chromosome structure.
